Protein: Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (P70600)
Organism: Rattus norvegicus (Rat)
Function: Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376' (By similarity). Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2 (By similarity).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:9645946}. Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane {ECO:0000269|PubMed:9645946}; Peripheral membrane protein {ECO:0000269|PubMed:9645946}; Cytoplasmic side {ECO:0000269|PubMed:9645946}. Cell projection, lamellipodium {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Nucleus {ECO:0000250}. Note=Colocalizes with integrins at the cell periphery. Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with PXN at the microtubule-organizing center. The tyrosine phosphorylated form is detected at cell-cell contacts (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell junction, focal adhesion. Note=Localizes to focal adhesions, but not isoform 1 and isoform 3.
Interaction partners:
- Proto-oncogene tyrosine-protein kinase Src
- Paxillin
- Breast cancer anti-estrogen resistance protein 1
- Src substrate cortactin
- Focal adhesion kinase 1
- Tyrosine-protein kinase Lyn
- Adapter molecule crk
- Guanine nucleotide-binding protein subunit alpha-12
- Transforming protein RhoA
- Integrin beta
Sequence:
MSGVSEPLSRVKVGTLRPPEGPPEPMVVVPVDVEKEDVRILKVCFYSNSFNPGKNFKLVKCTVQTEIQEIITSILLSGRIGPNIQLAECYGLRLKHMKSDEIHWLHPQMTVGEVQDKYECLHVEAEWRYDLQIRYLPEDFMESLKEDRTTLLYFYQQLRNDYMQRYASKVSEGMALQLGCLELRRFFKDMPHNALDKKSNFELLEKEVGLDLFFPKQMQENLKPKQFRKMIQQTFQQYASLREEECVMKFFNTLAGFANIDQETYRCELIQGWNITVDLVIGPKGIRQLTSQDTKPTCLAEFKQIRSIRCLPLEETQAVLQLGIEGAPQSLSIKTSSLAEAENMADLIDGYCRLQGEHKGSLIIHAKKDGEKRNSLPQIPTLNLESRRSHLSESCSIESDIYAEIPDETLRRPGGPQYGVAREDVVLNRILGEGFFGEVYEGVYTNHKGEKINVAVKTCKKDCTLDNKEKFMSEAVIMKNLDHPHIVKLIGIIEEEPTWIVMELYPYGELGHYLERNKNSLKVPTLVLYALQICKAMAYLESINCVHRDIAVRNILVASPECVKLGDFGLSRYIEDEDYYKASVTRLPIKWMSPESINFRRFTTASDVWMFAVCMWEILSFGKQPFFWLENKDVIGVLEKGDRLPKPELCPPVLYTLMTRCWDYDPSDRPRFTELVCSLSDIYQMERDIAIEQERNARYRPPKILEPTAFQEPPPKPSRPKYKHPPQTNLLAPKLQFQVPEGLCASSPTLTSPMEYPSPVNSLHTPPLHRHNVFKRHSMREEDFIRPSSREEAQQLWEAEKIKMRQVLDRQQKQMVEDSQWLRREERCLDPMVYMNDKSPLTPEKEAGYTEFTGPPQKPPRLGAQSIQPTANLDRTDDLVYHNVMTLVEAVLELKNKLSQLPPEEYVVVVKNVGLNLRKLIGSVDDLLPSLPASSRTEIEGTQKLLNKDLAELINKMRLAQQNAVTSLSEDCKRQMLTASHTLAVDAKNLLDAVDQAKVVANLAHPPAE