PTK2
Description
The PTK2 (protein tyrosine kinase 2) is a protein-coding gene located on chromosome 8.
PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around). It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.
== Function == The PTK2 gene encodes a cytosolic protein tyrosine kinase that is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases that included PYK2, but lacks significant sequence similarity to kinases from other subfamilies. It also includes a large FERM domain. With the exception of certain types of blood cells, most cells express FAK. FAK tyrosine kinase activity can be activated, which plays a key important early step in cell migration. FAK activity elicits intracellular signal transduction pathways that promote the turn-over of cell contacts with the extracellular matrix, promoting cell migration. FAK is required during development, with loss of FAK resulting in lethality. It seems to be a paradox that FAK is not absolutely required for cell migration, and may play other roles in the cell, including the regulation of the tumor suppressor p53.
PTK2, also known as Focal adhesion kinase (FAK), is a non-receptor protein-tyrosine kinase that plays a crucial role in regulating various cellular processes. It is essential for cell migration, adhesion, spreading, and the reorganization of the actin cytoskeleton. FAK is involved in the formation and disassembly of focal adhesions and cell protrusions, as well as cell cycle progression, proliferation, and apoptosis. It is required for early embryonic development, placenta development, and normal heart development. FAK also regulates axon growth and neuronal cell migration, branching, and synapse formation, playing a role in the development of the nervous system. Additionally, it contributes to osteogenesis and the differentiation of osteoblasts. FAK functions in integrin signal transduction and downstream signaling pathways initiated by various growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors, and LDL receptors. Upon activation, FAK forms multisubunit signaling complexes with SRC and SRC family members. This interaction leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors, and substrates. FAK regulates numerous signaling pathways, including the activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade, the activation of MAPK1/ERK2, MAPK3/ERK1, and the MAP kinase signaling cascade. It promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), modulating the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. FAK phosphorylates NEDD9 following integrin stimulation. It recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, thereby regulating P53/TP53 activity, ubiquitination, and proteasomal degradation. FAK phosphorylates SRC, increasing SRC kinase activity. Additionally, FAK phosphorylates ACTN1, ARHGEF7, GRB7, RET, and WASL. It also promotes phosphorylation of PXN and STAT1, likely by a SRC family kinase recruited to autophosphorylated PTK2/FAK1 rather than by PTK2/FAK1 itself. FAK promotes the phosphorylation of BCAR1, GIT2, and SHC1, which requires both SRC and PTK2/FAK1. Furthermore, it promotes the phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) lacks 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. FAK interacts with CAS family members, including BCAR1, BCAR3, and CASS4, through its first Pro-rich region. It also interacts with NEDD9 through its SH3 domain, and interacts with GIT1, SORBS1, ARHGEF28, and SHB. FAK is part of a complex containing THSD1, PTK2/FAK1, TLN1, and VCL. It interacts with PXN, TLN1, STAT1, DCC, WASL, ARHGEF7, GRB2, and GRB7. FAK is a component of a complex containing FER, CTTN, and PTK2/FAK1. It interacts with BMX, TGFB1I1, STEAP4, ZFYVE21, ESR1, PIK3R1 or PIK3R2, SRC, FGR, FLT4, and RET. FAK interacts with EPHA2 in resting cells. Activation of EPHA2 recruits PTPN11, leading to the dephosphorylation of PTK2/FAK1 and dissociation of the complex. FAK interacts with EPHA1 (kinase activity-dependent), CD4 (requires the presence of HIV-1 gp120), PIAS1, ARHGAP26, SHC1, RB1CC1 (inhibits PTK2/FAK1 activity and downstream signaling pathway activation), P53/TP53, MDM2, LPXN through its LD motif 3, MISP, CIB1 isoform 2, CD36, EMP2 (regulates PTK2 activation and localization), DSCAM, and AMBRA1. When tyrosine-phosphorylated, FAK interacts with tensin TNS1, and this interaction is enhanced by the phosphorylation of TNS1.
PTK2 is also known as FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71, p125FAK, pp125FAK.
