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Rabbit Anti-Phospho-Ack1 (Tyr859 + Tyr860)/FITC Conjugated antibody
background:
This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids SLCterminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq].
Function:
Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR (By similarity).
Subunit:
Homodimer. Interacts with CDC42. Interacts with CSPG4 (activated). Interacts with MERTK (activated); stimulates autophosphorylation. May interact (phosphorylated) with HSP90AB1; maintains kinase activity. Interacts with NPHP1. Interacts with SNX9 (via SH3 domain). Interacts with SRC (via SH2 and SH3 domain). Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts (via kinase domain) with AKT1. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2. Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 (By similarity).
Subcellular Location:
Cell membrane (By similarity). Nucleus (By similarity). Endosome (By similarity). Cell junction, adherens junction (By similarity). Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Cytoplasmic vesicle, clathrin-coated vesicle (By similarity). Membrane, clathrin-coated pit (By similarity). Note=The Tyr-284 phosphorylated form is found both in the membrane and nucleus. Co-localizes with EGFR on endosomes. Nuclear translocation is CDC42-dependent (By similarity).
Post-translational modifications:
Autophosphorylation regulates kinase activity. Phosphorylation on Tyr-518 is required for interaction with SRC and is observed during association with clathrin-coated pits (By similarity).
Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent (By similarity).
Similarity:
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Contains 1 protein kinase domain.
Contains 1 SH3 domain.
Contains 1 UBA domain.
Database links:
Entrez Gene: 303882 Rat
Entrez Gene: 280710 Cow
Entrez Gene: 10188 Human
Entrez Gene: 51789 Mouse
Omim: 606994 Human
SwissProt: Q17R13 Cow
SwissProt: Q07912 Human
SwissProt: O54967 Mouse
SwissProt: Q5U2X5 Rat
Unigene: 518513 Human
Unigene: 251115 Mouse
Unigene: 98335 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
Ack 1分子是一组促进酪氨酸激酶生长的家族成员，该蛋白与肿瘤分裂、生长、转移起到很重要的作用，可加速恶性肿瘤的浸润。
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