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 cytoplasmic protein tyrosine kinase that is involved in intracellular signaling pathways that control a wide range of cellular functions, including cell proliferation, survival, adhesion, and migration. FAK plays a crucial role in the cellular processes by which cells attach to and spread on the extracellular matrix (ECM), a process known as cell adhesion. This kinase is also implicated in the signaling pathways that regulate angiogenesis, cell cycle, and apoptosis (programmed cell death).

Structure

PTK2 protein consists of a central catalytic kinase domain flanked by large N- and C-terminal regions. The N-terminal region contains a FERM (band 4.1, ezrin, radixin, moesin) domain, which mediates direct binding to the cytoplasmic tail of integrins and to other proteins. The C-terminal region of PTK2 contains focal adhesion targeting (FAT) domain, which is involved in localizing PTK2 to focal adhesions - specialized structures that link the intracellular cytoskeleton to the ECM.

Function

The primary function of PTK2 is to integrate signals from the ECM and growth factors to promote cell movement and survival. Upon activation by integrin clustering or growth factor receptor activation, PTK2 undergoes autophosphorylation at Tyr397. This phosphorylation event creates a high-affinity binding site for Src family kinases, which further phosphorylate PTK2 at multiple sites, enhancing its kinase activity. Activated PTK2 phosphorylates a variety of downstream targets, including proteins involved in the reorganization of the actin cytoskeleton, such as paxillin and vinculin, which are critical for cell migration and adhesion.

Clinical Significance

Aberrant expression and activity of PTK2 have been observed in various types of cancer, where it is thought to contribute to cancer cell proliferation, survival, migration, and invasion. As such, PTK2 is considered a potential target for cancer therapy. Inhibitors of PTK2 kinase activity are currently being explored as therapeutic agents in preclinical and clinical trials for cancer treatment.

Research

Research on PTK2 has also implicated it in other diseases, including cardiovascular diseases and disorders of the nervous system. Its role in the regulation of cell adhesion and migration makes it a potential target for the development of treatments for diseases characterized by abnormal cell migration, such as chronic inflammation, vascular disease, and fibrosis.

See Also

• Cell signaling
• Protein kinase
• Cancer
• Integrin