
Gene Report
Approved Symbol | CDC42 |
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Approved Name | cell division cycle 42 |
Previous Name | "cell division cycle 42 (GTP-binding protein, 25kD)", "cell division cycle 42 (GTP binding protein, 25kDa)" |
Symbol Alias | G25K, CDC42Hs |
Name Alias | "GTP binding protein, 25kDa" |
Location | 1p36.1 |
Position | chr1:22418011-22419436 (+) |
External Links |
Entrez Gene: 998 Ensembl: ENSG00000070831 UCSC: uc001bfr.3 HGNC ID: 1736 |
No. of Studies (Positive/Negative) | 1(1/0)
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Type | Literature-origin |
Name in Literature | Reference | Research Type | Statistical Result | Relation Description | ![]() |
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CDC42 | Carvalho LA, 2014 | patients and normal controls | FC=1.6; P-value=0.002 | Thirty-four of the 47 monocyte inflammatory-related genes w...... Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls More... |
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Genetic/Epigenetic Locus | Protein and Other Molecule | Cell and Molecular Pathway | Neural System | Cognition and Behavior | Symptoms and Signs | Environment | MDD |
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3. The network is generated using Cytoscape Web

Gene mapped GO terms | ||||
ID | Name | Type | Evidence | |
---|---|---|---|---|
GO:0031256 | leading edge membrane | cellular component | IEA | |
GO:0031295 | T cell costimulation | biological process | TAS | |
GO:0035088 | establishment or maintenance of apical/basal cell polarity | biological process | IEA | |
GO:0003334 | keratinocyte development | biological process | IEA | |
GO:0042692 | muscle cell differentiation | biological process | TAS | |
GO:0051149 | positive regulation of muscle cell differentiation | biological process | TAS | |
GO:0048013 | ephrin receptor signaling pathway | biological process | TAS | |
GO:0048664 | neuron fate determination | biological process | IEA | |
GO:0031647 | regulation of protein stability | biological process | IEA | |
GO:0051835 | positive regulation of synapse structural plasticity | biological process | IEA | |
GO:0005525 | GTP binding | molecular function | IDA[15601624|23620790] | |
GO:0007163 | establishment or maintenance of cell polarity | biological process | TAS[11260256] | |
GO:0036464 | cytoplasmic ribonucleoprotein granule | cellular component | IDA[15121898] | |
GO:0051056 | regulation of small GTPase mediated signal transduction | biological process | TAS | |
GO:0051233 | spindle midzone | cellular component | IDA[15642749] | |
GO:0031333 | negative regulation of protein complex assembly | biological process | IPI[11584266] | |
GO:0032553 | ribonucleotide binding | molecular function | IEA | |
GO:0038096 | Fc-gamma receptor signaling pathway involved in phagocytosis | biological process | TAS | |
GO:0030742 | GTP-dependent protein binding | molecular function | IEA | |
GO:0005925 | focal adhesion | cellular component | IDA[21423176] | |
GO:0003161 | cardiac conduction system development | biological process | IEA | |
GO:0031274 | positive regulation of pseudopodium assembly | biological process | IDA[11035016] | |
GO:0032467 | positive regulation of cytokinesis | biological process | IMP[15642749] | |
GO:0007596 | blood coagulation | biological process | TAS | |
GO:0000139 | Golgi membrane | cellular component | ISS | |
GO:0030141 | secretory granule | cellular component | IEA | |
GO:0030036 | actin cytoskeleton organization | biological process | IDA[11035016] | |
GO:0070062 | extracellular exosome | cellular component | IDA[19056867|19199708|20458337|23376485|23533145] | |
GO:0007173 | epidermal growth factor receptor signaling pathway | biological process | TAS | |
GO:0043025 | neuronal cell body | cellular component | IDA[21048939] | |
GO:0010629 | negative regulation of gene expression | biological process | IEA | |
GO:0090316 | positive regulation of intracellular protein transport | biological process | IEA | |
GO:0045740 | positive regulation of DNA replication | biological process | IEA | |
GO:0061630 | ubiquitin protein ligase activity | molecular function | IDA[21435037] | |
GO:0031069 | hair follicle morphogenesis | biological process | IEA | |
GO:0045859 | regulation of protein kinase activity | biological process | IEA | |
GO:0005515 | protein binding | molecular function | IPI[7493928|9082982|9262406|9338791|9418861|9422512|9660763|9846874|10051605|10360578|10360579|10587647|10816584|10934474|11035016|11157984|11260256|11807099|11889037|12006984|12093730|12606577|12745076|12879077|14676191|15194684|15361624|15728724|1618951 | |
GO:0060684 | epithelial-mesenchymal cell signaling | biological process | IEA | |
GO:0051022 | Rho GDP-dissociation inhibitor binding | molecular function | IEA | |
GO:0005789 | endoplasmic reticulum membrane | cellular component | TAS | |
GO:0048554 | positive regulation of metalloenzyme activity | biological process | IEA | |
GO:0007264 | small GTPase mediated signal transduction | biological process | TAS | |
GO:0034332 | adherens junction organization | biological process | IEA | |
GO:0030175 | filopodium | cellular component | IDA[11035016] | |
GO:0043005 | neuron projection | cellular component | IDA[21048939] | |
GO:0042802 | identical protein binding | molecular function | IPI[9748241] | |
GO:0060661 | submandibular salivary gland formation | biological process | IEA | |
GO:0072686 | mitotic spindle | cellular component | IDA[15642749] | |
GO:1900026 | positive regulation of substrate adhesion-dependent cell spreading | biological process | IDA[11807099] | |
GO:0090135 | actin filament branching | biological process | IEA | |
GO:0032553 | ribonucleotide binding | molecular function | IEA | |
GO:0060501 | positive regulation of epithelial cell proliferation involved in lung morphogenesis | biological process | IEA | |
GO:0031435 | mitogen-activated protein kinase kinase kinase binding | molecular function | IEA | |
GO:0000322 | storage vacuole | cellular component | IEA | |
GO:0048010 | vascular endothelial growth factor receptor signaling pathway | biological process | TAS | |
GO:0042176 | regulation of protein catabolic process | biological process | IEA | |
GO:0051017 | actin filament bundle assembly | biological process | IEA | |
GO:0042059 | negative regulation of epidermal growth factor receptor signaling pathway | biological process | TAS | |
GO:0060071 | Wnt signaling pathway, planar cell polarity pathway | biological process | NAS[24431302] | |
GO:0035264 | multicellular organism growth | biological process | IEA | |
GO:0046330 | positive regulation of JNK cascade | biological process | IEA | |
GO:0007030 | Golgi organization | biological process | ISS | |
GO:0031424 | keratinization | biological process | IEA | |
GO:0007097 | nuclear migration | biological process | IEA | |
GO:0051489 | regulation of filopodium assembly | biological process | IDA[14978216] | |
GO:0051988 | regulation of attachment of spindle microtubules to kinetochore | biological process | IMP[15642749] | |
GO:0034613 | cellular protein localization | biological process | IEA | |
GO:0036336 | dendritic cell migration | biological process | IEA | |
GO:0005815 | microtubule organizing center | cellular component | IEA | |
GO:0072384 | organelle transport along microtubule | biological process | ISS | |
GO:0007411 | axon guidance | biological process | TAS | |
GO:0010628 | positive regulation of gene expression | biological process | IEA | |
GO:0043525 | positive regulation of neuron apoptotic process | biological process | IEA | |
GO:0034191 | apolipoprotein A-I receptor binding | molecular function | IPI[16443932] | |
GO:0045087 | innate immune response | biological process | TAS | |
GO:0046847 | filopodium assembly | biological process | IEA | |
GO:0005737 | cytoplasm | cellular component | IDA[11260256] | |
GO:0019901 | protein kinase binding | molecular function | IDA[19039103]; IPI[21048939] | |
GO:0043209 | myelin sheath | cellular component | IEA | |
GO:0060047 | heart contraction | biological process | IEA | |
GO:0032553 | ribonucleotide binding | molecular function | IEA | |
GO:0051683 | establishment of Golgi localization | biological process | ISS | |
GO:0031996 | thioesterase binding | molecular function | IPI[12612085] | |
GO:0007088 | regulation of mitotic nuclear division | biological process | IEA | |
GO:0090136 | epithelial cell-cell adhesion | biological process | IEA | |
GO:0043497 | regulation of protein heterodimerization activity | biological process | IEA | |
GO:0033138 | positive regulation of peptidyl-serine phosphorylation | biological process | IEA | |
GO:0030225 | macrophage differentiation | biological process | TAS[11260256] | |
GO:0060789 | hair follicle placode formation | biological process | IEA | |
GO:0016020 | membrane | cellular component | IDA[11807099|19946888] | |
GO:0005886 | plasma membrane | cellular component | IDA[11260256]; TAS | |
GO:0030307 | positive regulation of cell growth | biological process | IMP[21435037] | |
GO:0016567 | protein ubiquitination | biological process | IDA[21435037] | |
GO:0005829 | cytosol | cellular component | TAS | |
GO:0045177 | apical part of cell | cellular component | IEA | |
GO:0071338 | positive regulation of hair follicle cell proliferation | biological process | IEA | |
GO:0005911 | cell-cell junction | cellular component | IEA | |
GO:0021762 | substantia nigra development | biological process | IEP[22926577] | |
GO:0002040 | sprouting angiogenesis | biological process | IEA | |
GO:0043552 | positive regulation of phosphatidylinositol 3-kinase activity | biological process | IEA | |
GO:0060070 | canonical Wnt signaling pathway | biological process | IEA | |
GO:0003924 | GTPase activity | molecular function | TAS[11035016] | |
GO:0030496 | midbody | cellular component | IDA[15642749] |
Literature-origin KEGG pathway | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
hsa04360 | axon guidance | Axon guidance | Axon guidance represents a key stage in the formation of neu...... Axon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are read by growth cone receptors, and signal transduction pathways downstream of these receptors converge onto the Rho GTPases to elicit changes in cytoskeletal organization that determine which way the growth cone will turn. More... | |
hsa04510 | focal adhesion | Focal adhesion | Cell-matrix adhesions play essential roles in important biol...... Cell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the cell-extracellular matrix contact points, specialized structures are formed and termed focal adhesions, where bundles of actin filaments are anchored to transmembrane receptors of the integrin family through a multi-molecular complex of junctional plaque proteins. Some of the constituents of focal adhesions participate in the structural link between membrane receptors and the actin cytoskeleton, while others are signalling molecules, including different protein kinases and phosphatases, their substrates, and various adapter proteins. Integrin signaling is dependent upon the non-receptor tyrosine kinase activities of the FAK and src proteins as well as the adaptor protein functions of FAK, src and Shc to initiate downstream signaling events. These signalling events culminate in reorganization of the actin cytoskeleton; a prerequisite for changes in cell shape and motility, and gene expression. Similar morphological alterations and modulation of gene expression are initiated by the binding of growth factors to their respective receptors, emphasizing the considerable crosstalk between adhesion- and growth factor-mediated signalling. More... | |
hsa04810 | regulation of_actin_cytoskeleton | Regulation of actin cytoskeleton | ||
hsa04530 | tight junction | Tight junction | Epithelial tight junctions (TJs) are composed of at least th...... Epithelial tight junctions (TJs) are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic 'plaque' consisting of many different proteins that form large complexes. The transmembrane proteins mediate cell adhesion and are thought to constitute the intramembrane and paracellular diffusion barriers. The cytoplasmic 'plaque' contains three major multi-protein complexes consisting largely of scaffolding proteins, the ZO protein complex, the CRB3-Pals1-PATJ complex and the PAR-3-aPKC-PAR-6 complex. The ZO protein complex appears to organize the transmembrane proteins and couple them to other cytoplasmic proteins and to actin microfilaments. Two evolutionarily conserved protein complexes, the CRB3 and PAR complexes are involved in the establishment and maintenance of epithelial cell polarity. Besides these three protein complexes which seem to be constitutively associated at TJs, a number of proteins with different functions has been identified at TJs. These include additional scaffolding proteins like MUPP1 and MAGI-1, adaptor proteins, transcription regulators and RNA processing factors, regulatory proteins like small GTPases and G-proteins, kinases and phosphatases, and heat shock proteins. These are proposed to be involved in junction assembly, barrier regulation, gene transcription, and perhaps other, presently undefined pathways. More... |
Gene mapped KEGG pathways | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
hsa04666 | fc gamma_r_mediated_phagocytosis | Fc gamma R-mediated phagocytosis | Phagocytosis plays an essential role in host-defense mechani...... Phagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes take part in this process in higher organisms. After opsonization with antibodies (IgG), foreign extracellular materials are recognized by Fc gamma receptors. Cross-linking of Fc gamma receptors initiates a variety of signals mediated by tyrosine phosphorylation of multiple proteins, which lead through the actin cytoskeleton rearrangements and membrane remodeling to the formation of phagosomes. Nascent phagosomes undergo a process of maturation that involves fusion with lysosomes. The acquisition of lysosomal proteases and release of reactive oxygen species are crucial for digestion of engulfed materials in phagosomes. More... | |
hsa05120 | epithelial cell_signaling_in_helicobacter_pylori_infection | Epithelial cell signaling in Helicobacter pylori infection | Two major virulence factors of H. pylori are the vacuolating...... Two major virulence factors of H. pylori are the vacuolating cytotoxin (VacA) and the cag type-IV secretion system (T4SS) and its translocated effector protein, cytotoxin-associated antigen A (CagA). VacA binds to lipid rafts and glycosylphosphatidylinositol-anchored proteins (GPI-APs) of the target cell membrane. After insertion into the plasma membrane, VacA channels are endocytosed and eventually reach late endosomal compartments, increasing their permeability to anions with enhancement of the electrogenic vacuolar ATPase (v-ATPase) proton pump. In the presence of weak bases, osmotically active acidotropic ions will accumulate in the endosomes. This leads to water influx and vesicle swelling, an essential step in vacuole formation. In addition, it is reported that the VacA cleavage product binds to the tyrosine phosphatase receptor zeta (Ptprz) on epithelial cells and the induced signaling leads to the phosphorylation of the G protein-coupled receptor kinase-interactor 1 (Git1) and induces ulcerogenesis in mice. The other virulence factor cag T4SS mediates the translocation of the effector protein CagA, which is subsequently phosphorylated by a Src kinase. Phosphorylated CagA interacts with the protein tyrosine phosphatase SHP-2, thus stimulating its phosphatase activity. Activated SHP-2 is able to induce MAPK signalling through Ras/Raf-dependent and -independent mechanisms. Deregulation of this pathway by CagA may lead to abnormal proliferation and movement of gastric epithelial cells. More... | |
hsa04722 | neurotrophin signaling_pathway | Neurotrophin signaling pathway | Neurotrophins are a family of trophic factors involved in di...... Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory. More... | |
hsa05200 | pathways in_cancer | Pathways in cancer | ||
hsa04660 | t cell_receptor_signaling_pathway | T cell receptor signaling pathway | Activation of T lymphocytes is a key event for an efficient ...... Activation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. Engagement of these receptors through the interaction with a foreign antigen associated with major histocompatibility complex molecules and CD28 counter-receptors B7.1/B7.2, respectively, results in a series of signaling cascades. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions, leading to T-cell proliferation, cytokine production and differentiation into effector cells. More... | |
hsa05211 | renal cell_carcinoma | Renal cell carcinoma | Renal cell carcinoma (RCC) is a heterogenous term comprising...... Renal cell carcinoma (RCC) is a heterogenous term comprising a group of neoplasms of renal origin. There are 4 major histologic subtypes of RCC: conventional (clear cell RCC, 75%), papillary (15%), chromophobic (5%), and collecting duct (2%). Multiple genes are involved in the molecular pathogenesis of RCC. VHL is a tumor suppressor gene responsible for hereditary (von Hippel-Lindau) and sporadic variants of conventional (clear cell) RCC. In the absence of VHL, hypoxia-inducible factor alpha (HIF-alpha) accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. An oncogene, MET has been found to be mutant in cases of hereditary papillary renal cancer (HPRC), although the incidence of c-MET mutations is low in sporadic papillary RCC. Once activated, MET mediates a number of biological effects including motility, invasion of extracellular matrix, cellular transformation, prevention of apoptosis and metastasis formation. Mutations in the fumarate hydratase (FH) gene cause hereditary leiomyomatosis and renal cancer syndrome (HLRCC) papillary renal tumors, although the incidence of FH mutations in sporadic tumors is unknown. Loss of functional FH leads to accumulation of fumarate in the cell, triggering inhibition of HPH and preventing targeted pVHL-mediated degradation of HIF-alpha. BHD mutations cause the Birt-Hogg-Dube syndrome and its associated chromophobe, hybrid oncocytic, and conventional (clear cell) RCC. The incidence of BHD mutations in sporadic renal tumors is not known. More... | |
hsa04144 | endocytosis | Endocytosis | Endocytosis is a mechanism for cells to remove ligands, nutr...... Endocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins entering through clathrin-dependent endocytosis (CDE) have sequences in their cytoplasmic domains that bind to the APs (adaptor-related protein complexes) and enable their rapid removal from the PM. In addition to APs and clathrin, there are numerous accessory proteins including dynamin. Depending on the various proteins that enter the endosome membrane, these cargoes are sorted to distinct destinations. Some cargoes, such as nutrient receptors, are recycled back to the PM. Ubiquitylated membrane proteins, such as activated growth-factor receptors, are sorted into intraluminal vesicles and eventually end up in the lysosome lumen via multivesicular endosomes (MVEs). There are distinct mechanisms of clathrin-independent endocytosis (CIE) depending upon the cargo and the cell type. More... | |
hsa04010 | mapk signaling_pathway | MAPK signaling pathway | The mitogen-activated protein kinase (MAPK) cascade is a hig...... The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli. More... | |
hsa05212 | pancreatic cancer | Pancreatic cancer | Normal duct epithelium progresses to infiltrating cancer thr...... Normal duct epithelium progresses to infiltrating cancer through a series of histologically defined precursors (PanINs). The overexpression of HER-2/neu and activating point mutations in the K-ras gene occur early, inactivation of the p16 gene at an intermediate stage, and the inactivation of p53, SMAD4, and BRCA2 occur relatively late. Activated K-ras engages multiple effector pathways. Although EGF receptors are conventionally regarded as upstream activators of RAS proteins, they can also act as RAS signal transducers via RAS-induced autocrine activation of the EGFR family ligands. Pancreatic ductal adenocarcinoma (PDA) show elevated expression of EGF receptors (e.g. HER2/neu) and their ligands (e.g.TGF-alpha) consistent with the presence of this autocrine loop. Moreover, PDA shows extensive genomic instability and aneuploidy. Telomere attrition and mutations in p53 and BRCA2 are likely to contribute to these phenotypes. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the inhibitory influence of the transforming growth factor-beta signalling pathway. More... | |
hsa04670 | leukocyte transendothelial_migration | Leukocyte transendothelial migration | Leukocyte migaration from the blood into tissues is vital fo...... Leukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (CAM) and then migrate across the vascular endothelium. A leukocyte adherent to CAMs on the endothelial cells moves forward by leading-edge protrusion and retraction of its tail. In this process, alphaL /beta2 integrin activates through Vav1, RhoA, which subsequently activates the kinase p160ROCK. ROCK activation leads to MLC phosphorylation, resulting in retraction of the actin cytoskeleton. Moreover, Leukocytes activate endothelial cell signals that stimulate endothelial cell retraction during localized dissociation of the endothelial cell junctions. ICAM-1-mediated signals activate an endothelial cell calcium flux and PKC, which are required for ICAM-1 dependent leukocyte migration. VCAM-1 is involved in the opening of the endothelial passage through which leukocytes can extravasate. In this regard, VCAM-1 ligation induces NADPH oxidase activation and the production of reactive oxygen species (ROS) in a Rac-mediated manner, with subsequent activation of matrix metallopoteinases and loss of VE-cadherin-mediated adhesion. More... | |
hsa04520 | adherens junction | Adherens junction | Cell-cell adherens junctions (AJs), the most common type of ...... Cell-cell adherens junctions (AJs), the most common type of intercellular adhesions, are important for maintaining tissue architecture and cell polarity and can limit cell movement and proliferation. At AJs, E-cadherin serves as an essential cell adhesion molecules (CAMs). The cytoplasmic tail binds beta-catenin, which in turn binds alpha-catenin. Alpha-catenin is associated with F-actin bundles directly and indirectly. The integrity of the cadherin-catenin complex is negatively regulated by phosphorylation of beta-catenin by receptor tyrosine kinases (RTKs) and cytoplasmic tyrosine kinases (Fer, Fyn, Yes, and Src), which leads to dissociation of the cadherin-catenin complex. Integrity of this complex is positively regulated by beta -catenin phosphorylation by casein kinase II, and dephosphorylation by protein tyrosine phosphatases. Changes in the phosphorylation state of beta-catenin affect cell-cell adhesion, cell migration and the level of signaling beta-catenin. Wnt signaling acts as a positive regulator of beta-catenin by inhibiting beta-catenin degradation, which stabilizes beta-catenin, and causes its accumulation. Cadherin may acts as a negative regulator of signaling beta-catenin as it binds beta-catenin at the cell surface and thereby sequesters it from the nucleus. Nectins also function as CAMs at AJs, but are more highly concentrated at AJs than E-cadherin. Nectins transduce signals through Cdc42 and Rac, which reorganize the actin cytoskeleton, regulate the formation of AJs, and strengthen cell-cell adhesion. More... | |
hsa04370 | vegf signaling_pathway | VEGF signaling pathway | There is now much evidence that VEGFR-2 is the major mediato...... There is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic angiogenesis. The binding of VEGF to VEGFR-2 leads to a cascade of different signaling pathways, resulting in the up-regulation of genes involved in mediating the proliferation and migration of endothelial cells and promoting their survival and vascular permeability. For example, the binding of VEGF to VEGFR-2 leads to dimerization of the receptor, followed by intracellular activation of the PLCgamma;PKC-Raf kinase-MEK-mitogen-activated protein kinase (MAPK) pathway and subsequent initiation of DNA synthesis and cell growth, whereas activation of the phosphatidylinositol 3' -kinase (PI3K)-Akt pathway leads to increased endothelial-cell survival. Activation of PI3K, FAK, and p38 MAPK is implicated in cell migration signaling. More... | |
hsa04062 | chemokine signaling_pathway | Chemokine signaling pathway | Inflammatory immune response requires the recruitment of leu...... Inflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for the cell trafficking and thus are vital for protective host response. In addition, chemokines regulate plethora of biological processes of hematopoietic cells to lead cellular activation, differentiation and survival. The chemokine signal is transduced by chemokine receptors (G-protein coupled receptors) expressed on the immune cells. After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. Various members of small GTPases are involved in this process. Induction of nitric oxide and production of reactive oxygen species are as well regulated by chemokine signal via calcium mobilization and diacylglycerol production. More... | |
hsa04912 | gnrh signaling_pathway | GnRH signaling pathway | Gonadotropin-releasing hormone (GnRH) secretion from the hyp...... Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes. More... | |
hsa05130 | pathogenic escherichia_coli_infection | Pathogenic Escherichia coli infection | Eenteropathogenic E. coli (EPEC) and enterohemorrhagic E. co...... Eenteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections is induction of attaching and effacing (A/E) lesions that damage intestinal epithelial cells. The capacity to form A/E lesions is encoded mainly by the locus of enterocyte effacement (LEE) pathogenicity island. Tir, Map, EspF, EspG are known LEE-encoded effector proteins secreted via the type III secretion system, which is also LEE-encoded, into the host cell. EPEC and EHEC Tir's link the extracellular bacterium to the cell cytoskeleton. Map and EspF are involved in mitochondrion membrane permeabilization. EspG interacts with tubulins and stimulates microtubule destabilization. LEE-encoded adhesin or intimin (Eae) is exported via the general secretory pathway to the periplasm, where it is inserted into the outer membrane. In addition to Tir, two potential host cell-carried intimin receptors, beta1 integrin (ITGB1) and nucleolin (NCL), have so far been identified. The distinguishing feature of EHEC is the elaboration of Shiga-like toxin (Stx). Stx cleaves ribosomal RNA, thereby disrupting protein synthesis and killing the intoxicated epithelial or endothelial cells. More... |
Gene mapped BioCarta pathways | ||||
ID | Name | Brief Description | Full Description | |
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SALMONELLA_PATHWAY | salmonella pathway | How does salmonella hijack a cell | Pathogenic Salmonella enter cells such as those of the intes...... Pathogenic Salmonella enter cells such as those of the intestinal epithelium by altering cellular cytoskeletal structure and inducing membrane ruffling of the infected cell. Salmonella is able to alter the cytoskeleton and membrane through the action of secreted bacterial Sip proteins, SopE, SopB, and SptP that are inserted into the cytosol of the infected cell. Sip proteins encoded by Salmonella are required for the action of SopE and for the invasion of epithelial cells. SipA stabilizes actin filaments, inducing membrane ruffling and perhaps focusing membrane changes where bacteria are localized to allow their entry. SipC produces a similar effect on actin filaments and cytoskeletal structure. SopE acts as an exchange factor on Rac1 and Cdc42, two GTPases in the Rho family that regulate actin cytoskeleton. The activation of Rac2 and Cdc42 by Salmonella SopE induces changes in cytoskeleton structure that allow bacterial entry into the cell. SopB is another salmonella protein that acts as an inositol polyphosphate phosphatase and also stimulates Cdc42 and Rac1. One of the cellular targets of both Cdc42 and Rac1 that affects actin structure is the Arp2/3 complex. Cdc42 and Rac1 activate Wasp, which activates Arp2/3. Activated Arp2/3 induces the formation of actin Y branches, which in combination with changes in actin caused by SipA and SipC help to form lamellipodia, and causes membrane ruffling, leading to entry of Salmonella into the affected cell. After the initial infection, cells quickly return to their normal morphology, a process that depends on the action of the bacterial protein SptP. While SopE acts as an exchange factor, SptP acts as a GTPase activating protein to inactivate Rac1 and Cdc42 once again. This inactivation of the original entry mechanism provides an example of the delicate balance between infectious organisms and their host. More... | |
CDC42RAC_PATHWAY | cdc42rac pathway | Role of PI3K subunit p85 in regulation of Actin Organization and Cell Migration | Migration of cells is involved in essential functions such a...... Migration of cells is involved in essential functions such as development, invasiveness of cancer cells, leukocyte movement toward chemotactic signals, and fibroblast response to injury. Cells can migrate in a specific direction in response to extracellular signals through pathways that trigger changes in the cytoskeleton, particularly actin filaments, increasing lamellipodia and filopodia formation and decreasing focal adhesions. Factors like PDGF activate PI3 kinase and multiple pathways downstream to stimulate cell migration. One pathway regulating migration through the p85 regulatory subunit of PI3 kinase does not require PI3-kinase activity. In this pathway, p85 of PI3-kinase activates cdc42, which activates N-Wasp (Wiskott-Aldrich Syndrome Protein) to regulate ARP-2/3. ARP-2/3 is a complex of proteins localized at the leading edge of moving cells that nucleates the formation of new actin fibers and interacts with Wasp to stimulate migration. The cdc42 pathway also regulates p21-activate kinase 1 (PAK1). Another pathway by which PI3 kinase regulates migration is through the small GTPase Rac. PAK1 is a downstream target of Rac as well as cdc42. Downstream of Rac and PAK1, Myosin light chain kinase (MLCK) phosphorylates myosin light chain to increase cell migration. The regulation of the localization and activity of signaling factors creates coordinated pathways linking extracellular signals and cellular migration. More... | |
RAS_PATHWAY | ras pathway | Ras Signaling Pathway | Ras activates many signaling cascades. Here we illustrate so...... Ras activates many signaling cascades. Here we illustrate some of the well-characterized cascades in a generic compilation of effector molecules. The effectors mediate Ras stimulation to a diverse set of cellular signals. Many of these signals are interpreted differently depending on the cell type or microenvironment receiving the stimulus. Not all of these effectors are activated in any given cell type. The primary method of activation is to promote the translocation of the molecule to the plasma membrane where additional interactions lead to the activation of the molecule. RalGDS is a Guanine Exchange Factor (GEF) for Ral but also has other independent functions. RalGDS activates RalA/B-related small GTPases. RalBP1 is a GTPase activating protein that leads to the inhibition of the Rac and CDC42 GTPases. Ral can also interact with phospholipase D1 (PLD1) that can also be activated by RhoA. Ras stimulation of the lipid kinase activity of PI3K occurs through an interaction with the p110 catalytic subunit. PI3K phosphorylates the D3 position of phosphatidylinositides. In this example Pip2 is converted to PIP3. PIP3 stimulates the AKT/PKB kinase and several of the Rac-GEFs such as Sos1 AND Vav. AKT activation inhibits apoptosis by inhibiting the actions of Bad, Caspase9 and AFX. AKT further hinders apoptosis by phosphorylating the IkB repressor of NFkB. Stimulus of Rac causes among other things the activation of NFkB. Ras also stimulates the mitogen-activated kinases ERK1/2 via the Raf1 cascade. The Erk kinases translocate to the nucleus where they phosphorylate various transcription factors such as ELK1 More... | |
AGR_PATHWAY | agr pathway | Agrin in Postsynaptic Differentiation | The heparan sulphate proteoglycan agrin is well known as the...... The heparan sulphate proteoglycan agrin is well known as the key assembly factor of postsynaptic differentiation at the neuromuscular junction (NMJ), but recent data suggest it also plays a direct role in the organization of the cytoskeleton in the skeletal muscle. Signaling through muscle-specific proteins such as muscle specific kinase (MuSK) and or acetylcholine receptor (AchRs)/rapsyn, agrin can activate ubiquitously expressed Rac, Cdc42, and p21-activated kinase (PAK) that are involved in actin polymerization. Agrin also engages signaling pathways of several potent oncogenes (i.e., SFK, ErbB receptors, and cortactin). More... | |
P38MAPK_PATHWAY | p38mapk pathway | p38 MAPK Signaling Pathway | p38 MAPKs are members of the MAPK family that are activated ...... p38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases of the Rho family (Rac, Rho, Cdc42). As with other MAPK cascades, the membrane-proximal component is a MAPKKK, typically a MEKK or a mixed lineage kinase (MLK). The MAPKKK phosphorylates and activated MKK3/5, the p38 MAPK kinase. MKK3/6 can also be activated directly by ASK1, which is stimulated by apoptotic stimuli. P38 MAK is involved in regulation of Hsp27 and MAPKAP-2 and several transcription factors including ATF2, STAT1, THE Max/Myc complex, MEF-2, ELK-1 and indirectly CREB via activation of MSK1. More... | |
MAL_PATHWAY | mal pathway | Role of MAL in Rho-Mediated Activation of SRF | Serum response factor (SRF) is a transcription factor, which...... Serum response factor (SRF) is a transcription factor, which binds to a serum response element (SRE) associated with a variety of genes including (i)immediate early genes such as c-fos, fosB, junB, egr-1 and -2, (ii)neuronal genes such as nurr1 and nur77, and (iii)muscle genes such as actins and myosins. By regulating expression of these genes, SRF controls cell growth and differentiation, neuronal transmission as well as muscle development and function. SRF can be activated by serum, lysophosphatidic acid (LPA), lipopolysaccharide (LPS), 12-O-tetradecanoylphorbol-13-acetate (TPA), cytokines, tumor necrosis factor-alpha (TNFalpha), agents that increase intracellular Ca2+, T-cell virus1 activator protein, hepatitis B virus activator proteins pX, activated oncogenes and protooncogenes and extracellular stimuli such as antioxidant and UV light. In serum-starved cells, MAL is predominantly cytoplasmic where it is sequestered by actin monomers. Upon serum stimulation, Rho becomes active and, through its interaction with ROCK and mDia1, causes an accumulation of F-actin and a commensurate decrease in the level of G-actin. As a consequence, MAL is no longer sequestered and is free to translocate to the nucleus where it associates with SRF and activates SRE-mediated gene expression. More... |
Gene mapped Reactome pathways | |||
ID | Name | Description | |
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REACT_18407 | g alpha_12_13_signalling_events | The alpha subunits of G12 and 13 bind RhoGEFs (guanine nucle...... The alpha subunits of G12 and 13 bind RhoGEFs (guanine nucleotide exchange factors, which activate small G proteins) providing a path to Rho-mediated cytoskeletal responses that are likely involved in shape change in platelets. More... | |
REACT_11051 | rho gtpase_cycle | The cycling of Rho GTPases is tightly controlled by three cl...... The cycling of Rho GTPases is tightly controlled by three classes of protein. These are. More... | |
REACT_12484 | egfr downregulation | Regulation of receptor tyrosine kinase (RTK) activity is imp...... Regulation of receptor tyrosine kinase (RTK) activity is implicated in the control of almost all cellular functions. One of the best understood RTKs is epidermal growth factor receptor (EGFR). Growth factors can bind to EGFR and activate it to initiate signalling cascades within the cell. EGFRs can also be recruited to clathrin-coated pits which can be internalised into endocytic vesicles. From here, EGFRs can either be recycled back to the plasma membrane or directed to lysosomes for destruction.This provides a mechanism by which EGFR signalling is negatively regulated and controls the strength and duration of EGFR-induced signals. It also prevents EGFR hyperactivation as commonly seen in tumorigenesis. The proto-oncogene Cbl can negatively regulate EGFR signalling. The Cbl family of RING-type ubiquitin ligases are able to poly-ubiquitinate EGFR, an essential step in EGFR degradation. All Cbl proteins have a unique domain that recognises phosphorylated tyrosine residues on activated EGFRs. They also direct the ubiquitination and degradation of activated EGFRs by recruiting ubiquitin-conjugation enzymes. Cbl proteins function by specifically targeting activated EGFRs and mediating their down-regulation, thus providing a means by which signaling processes can be negatively regulated. Cbl also promotes receptor internalization via it's interaction with an adaptor protein, CIN85 (Cbl-interacting protein of 85kDa). CIN85 binds to Cbl via it's SH3 domain and is enhanced by the EGFR-induced tyrosine phosphorylation of Cbl. The proline-rich region of CIN85 interacts with endophilins which are regulatory components of clathrin-coated vesicles (CCVs). Endophilins bind to membranes and induce membrane curvature, in conjunction with other proteins involved in CCV formation. The rapid recruitment of endophilin to the activated receptor complex by CIN85 is the mechanism which controls receptor internalization. More... | |
REACT_19183 | cd28 co_stimulation | In naive T cells, CD28 costimulation enhances cell cycle ent...... In naive T cells, CD28 costimulation enhances cell cycle entry, potently stimulates expression of both the mitogenic lymphokine interleukin-2 (IL-2) and its receptor, and stimulates the activation of an antiapoptotic program. CD28 engages with one or both members of the B7 receptor family, B7.1 and B7.2. Upon ligand binding the tyrosines and proline-rich motifs present in the cytoplasmic tail of CD28 are phosphorylated by Lck or Fyn. Upon phosphorylation CD28 recruits and induces phosphorylation and activation of a more restricted set of intracellular signaling components that, together with those mobilized by the TCR, contribute to convert membrane-based biochemical and biophysical changes into gene activation events. Proteins like PI3K, Vav-1, Tec and Itk kinases, AKT, and the Dok-1 adaptor have been identified as elements of the CD28 signaling pathway by biochemical or genetic approaches or both. More... | |
REACT_21303 | myogenessis | ||
REACT_9417 | signaling by_egfr | The epidermal growth factor receptor (EGFR) is one member of...... The epidermal growth factor receptor (EGFR) is one member of the ErbB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands leads to autophosphorylation of tyrosine residues on the receptor and subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. Ligand binding with EGFR results in receptor homo- or heterodimerization at the cell surface. Trans-autophosphorylation of the EGFR tyrosine kinase domains occurs and the phosphorylated tyrosine kinase residues serve as binding sites for the recruitment of signal transducers and activators of intracellular substrates, such as Ras, which then stimulate an intracellular signal transduction cascade. More... | |
REACT_19259 | sema4d in_semaphorin_signaling | Semaphorin 4D (Sema 4D/CD100) is an axon guidance molecule w...... Semaphorin 4D (Sema 4D/CD100) is an axon guidance molecule with two disulfide-linked 150-kDa subunits. SEMA4D is structurally defined by a conserved 500-amino acid extracellular domain with 16 cysteines (sema domain) and also an Ig-like domain C-terminal to the sema domain. Sema4D is expressed on the cell surface as a homodimer; cysteine 679 within the sema domain is required for this dimerization. The main receptors for Sema4D are plexin-B1 and CD72. The activation of plexins by semaphorins initiates a variety of signaling processes that involve several small GTPases of the Ras and Rho families. Sema4D-Plexin-B1 interaction appears to mediate different and sometimes opposite effects depending on the cellular context. Plexin-B1 activation inhibits integrin-mediated cell attachment and cell migration through the activation of the R-RasGAP activity inherent to plexin-B1 or through the inhibition of RhoA. However, activation of plexin-B1 by Sema4D stimulates the migration of endothelial cells by mediating the activation of RhoA. More... | |
REACT_19351 | signaling by_robo_receptor | The Roundabout (Robo) family encodes transmembrane receptors...... The Roundabout (Robo) family encodes transmembrane receptors that regulate axonal guidance and cell migration. The major function of the Robo receptors is to mediate repulsion of the navigating growth cones. There are four human Robo homologues, Robo1, Robo2, Robo3 and Robo4. Most of the Robos have the similar ectodomain architecture as the cell adhesion molecules, five Ig domains followed by three FN3 repeats except for Robo4, it has 2Ig and 2FN3 repeats. The cytoplasmic domains of Robo receptors are in general poorly conserved. However, there are four short conserved cytoplasmic sequence motifs, named CC0-3, that serve as binding sites for adaptor proteins. The ligands for the human Robo receptors are the three Slit proteins Slit1, Slit2, and Slit3; all of the Slit proteins contain a tandem of four LRR (leucine rich repeat) domains at N terminus, termed D1 D4 followed by six EGF (epidermal growth factor)-like domains, a laminin G like domain (ALPS), three EGF-like domains, and a C-terminal cysteine knot domain. Most Slit proteins are cleaved within the EGF-like region by unknown proteases. Slit protein binding modulates Robo interactions with the cytosolic adaptors. The cytoplasmic domain of Robo1 and Robo2 determines the repulsive responses of these receptors. Based on the studies from both invertebrate and vertebrate organisms its been inferred that Robo induces growth cone repulsion by controlling cytoskeletal dynamics via either Abelson kinase (Abl) and Enabled (Ena), or Rac activity. More... | |
REACT_6900 | signaling in_immune_system | Humans are exposed to millions of potential pathogens daily,...... Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system. More... | |
REACT_19271 | semaphorin interactions | Semaphorins are a large family of cell surface and secreted ...... Semaphorins are a large family of cell surface and secreted guidance molecules divided into eight classes on the basis of their structures. They all have an N-terminal conserved sema domain. Semaphorins signal through multimeric receptor complexes that include other proteins such as plexins and neuropilins. More... | |
REACT_18266 | axon guidance | Axon guidance / axon pathfinding is the process by which neu...... Axon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, which senses the guidance cues in the environment through guidance cue receptors and responds by undergoing cytoskeletal changes that determine the direction of axon growth. Guidance cues present in the surrounding environment provide the necessary directional information for the trip. These extrinsic cues have been divided into attractive or repulsive signals that tell the growth cone where and where not to grow. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules and their receptors that guide axons. These include netrins, Slits, semaphorins, and ephrins, and their cognate receptors, DCC and or uncoordinated-5 (UNC5), roundabouts (Robo), neuropilin and Eph. In addition, many other classes of adhesion molecules are also used by growth cones to navigate properly which include NCAM and L1CAM. More... | |
REACT_19277 | sema4d induced_cell_migration_and_growth_cone_collapse | Sema4D-mediated attraction of endothelial cells requires Rho...... Sema4D-mediated attraction of endothelial cells requires Rho, but not R-Ras, signaling. Sema4D-mediated plexinB1 activation activates Rho and its downstream effector ROCK. ROCK then phosphorylates MLC to induce actomyosin stress fiber contraction and to direct the assembly of focal adhesion complexes and integrin-mediated adhesion. More... | |
REACT_19184 | downstream events_in_gpcr_signaling | G protein-coupled receptors. The beta:gamma G-protein dimer ...... G protein-coupled receptors. The beta:gamma G-protein dimer is also involved in downstream signaling , and some receptors form part of metastable complexes of receptor and accessory proteins such as the arrestins. GPCRs are involved in many diverse signaling events , using a variety of pathways that include modulation of adenylyl cyclase, phospholipase C, the mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK) c-Jun-NH2-terminal kinase (JNK) and p38 MAPK. More... | |
REACT_19238 | cd28 dependent_vav1_pathway | CD28 binds to several intracellular proteins including PI3 k...... CD28 binds to several intracellular proteins including PI3 kinase, Grb-2, Gads and ITK. Grb-2 specifically co-operates with Vav-1 in the up-regulation of NFAT/AP-1 transcription. CD28 costimulation resulted in a prolonged and sustained phosphorylation and membrane localization of Vav1 in comparison to T-cell receptor activation alone. Tyrosine-phosphorylated Vav1 is an early point of integration between the signaling routes triggered by the T-cell receptor and CD28. Vav1 transduces TCR and co-stimulatory signals to multiple biochemical pathways and several cytoskeleton-dependent processes. The products of Vav1 activation, Rac1 and Cdc42, in turn activate the mitogen-activated protein kinases JNK and p38. Vav1 is also required for TCR-induced calcium flux, activation of the ERK MAP kinase pathway, activation of the NF-kB transcription factor, inside-out activation of the integrin LFA-1, TCR clustering, and polarisation of the T cell. More... | |
REACT_19344 | costimulation by_the_cd28_family | Optimal activation of T-lymphocytes requires at least two si...... Optimal activation of T-lymphocytes requires at least two signals. A primary one is delivered by the T-cell receptor (TCR) complex after antigen recognition and additional costimulatory signals are delivered by the engagement of costimulatory receptors such as CD28. The best-characterized costimulatory pathways are mediated by a set of cosignaling molecules belonging to the CD28 superfamily, including CD28, CTLA4, ICOS, PD1 and BTLA receptors. These proteins deliver both positive and negative second signals to T-cells by interacting with B7 family ligands expressed on antigen presenting cells. Different subsets of T-cells have very different requirements for costimulation. CD28 family mediated costimulation is not required for all T-cell responses in vivo, and alternative costimulatory pathways also exist. Different receptors of the CD28 family and their ligands have different regulation of expression. CD28 is constitutively expressed on naive T cells whereas CTLA4 expression is dependent on CD28/B7 engagement and the other receptor members ICOS, PD1 and BTLA are induced after initial T-cell stimulation. The positive signals induced by CD28 and ICOS molecules are counterbalanced by other members of the CD28 family, including cytotoxic T-lymphocyte associated antigen (CTLA)4, programmed cell death (PD)1, and B and T lymphocyte attenuator (BTLA), which dampen immune responses. The balance of stimulatory and inhibitory signals is crucial to maximize protective immune responses while maintaining immunological tolerance and preventing autoimmunity. The costimulatory receptors CD28, CTLA4, ICOS and PD1 are composed of single extracellular IgV-like domains, whereas BTLA has one IgC-like domain. Receptors CTLA4, CD28 and ICOS are covalent homodimers, due to an interchain disulphide linkage. The costimulatory ligands B71, B72, B7H2, B7H1 and B7DC, have a membrane proximal IgC-like domain and a membrane distal IgV-like domain that is responsible for receptor binding and dimerization. CD28 and CTLA4 have no known intrinsic enzymatic activity. Instead, engagement by their physiologic ligands B71 and B72 leads to the physical recruitment and activation of downstream T-cell effector molecules. More... |
