PTK2
GeneName
PTK2
Summary
PTK2, also known as FAK (focal adhesion kinase), pp125FAK, or FRNK, is a 119 kDa non-membrane spanning protein tyrosine kinase that plays a pivotal role in cellular processes such as adhesion, migration, and proliferation. It is predominantly localised at focal adhesions, cell membranes, and the cytoskeleton, and is involved in various signalling pathways including integrin-mediated signalling and angiogenesis. PTK2 is crucial for the regulation of cell motility and shape, and it participates in the phosphorylation of proteins that modulate cell adhesion and migration dynamics. Its activity is regulated by binding to various proteins, including integrins and other kinases, and it is implicated in processes such as heart morphogenesis and wound healing.
Importance
PTK2 is relevant to: - Cancer research due to its role in cell migration and invasion, which are critical for metastasis - Tissue repair and regeneration as it regulates wound healing and cellular responses to injury - Developmental biology through its involvement in heart morphogenesis and angiogenesis - Neurological research for its role in axon guidance and neuronal cell signalling - Vascular biology, particularly in the context of endothelial cell migration and response to shear stress
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Abcam Product Citation Summary
The data indicates that PTK2 is being studied in various contexts, particularly in relation to cancer, cell migration, and the FA pathway. The majority of the experiments were conducted using mouse models, with a focus on breast cancer brain metastases and the activation of the FA pathway. Additionally, human samples and endothelial cells were also examined, highlighting the relevance of PTK2 in both animal models and human biology.
Abcam Product Citation Table
Developmental stage
Isoform 6
Detected in cultured cells, immediately after seeding and before formation of focal adhesions (at protein level).
Domain
The Pro-rich regions interact with the SH3 domain of CAS family members, such as BCAR1 and NEDD9, and with the GTPase activating protein ARHGAP26.
The C-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions.
Function
Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. 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 the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.
Isoform 6
Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.
Involvement in disease
Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.
Post-translational modifications
Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-925, even when cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated only when cells are adherent. Phosphorylation at Tyr-397 is important for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-925 is important for interaction with GRB2. Dephosphorylated by PTPN11; PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). Microtubule-induced dephosphorylation at Tyr-397 is crucial for the induction of focal adhesion disassembly; this dephosphorylation could be catalyzed by PTPN11 and regulated by ZFYVE21. Phosphorylation on tyrosine residues is enhanced by NTN1 (By similarity).
Sumoylated; this enhances autophosphorylation.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.
Tissue Specificity
Detected in B and T-lymphocytes. Isoform 1 and isoform 6 are detected in lung fibroblasts (at protein level). Ubiquitous. Expressed in epithelial cells (at protein level) (PubMed:31630787).
Cellular localization
- Cell junction
- Focal adhesion
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasm
- Perinuclear region
- Cytoplasm
- Cell cortex
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Nucleus
- Cytoplasm
- Cytoskeleton
- Cilium basal body
- Cytoplasm
- Constituent of focal adhesions. Detected at microtubules.
Alternative names
FAK, FAK1, PTK2, Focal adhesion kinase 1, FADK 1, Focal adhesion kinase-related nonkinase, Protein phosphatase 1 regulatory subunit 71, Protein-tyrosine kinase 2, p125FAK, pp125FAK, FRNK, PPP1R71