C-src tyrosine kinase

C-src Tyrosine Kinase

C-src tyrosine kinase is a non-receptor tyrosine kinase that is encoded by the SRC gene in humans. It is a member of the Src family of kinases (SFKs), which are involved in the regulation of various cellular processes, including growth, differentiation, survival, and migration. C-src is ubiquitously expressed in many tissues and plays a critical role in signal transduction pathways.

Structure

C-src is a 60 kDa protein that consists of several distinct domains:

• The SH3 domain (Src Homology 3) is involved in protein-protein interactions by binding to proline-rich motifs.
• The SH2 domain (Src Homology 2) binds to phosphorylated tyrosine residues on target proteins, facilitating the recruitment of c-src to activated receptors and other signaling proteins.
• The kinase domain is responsible for the enzymatic activity of c-src, transferring a phosphate group from ATP to tyrosine residues on substrate proteins.
• The regulatory tail contains a tyrosine residue (Y527 in humans) that, when phosphorylated, inhibits the kinase activity of c-src.

Function

C-src is involved in the regulation of several cellular processes:

• Cell growth and proliferation: C-src is activated by growth factor receptors and integrins, leading to the activation of downstream signaling pathways such as the MAPK/ERK pathway.
• Cell adhesion and migration: C-src modulates the dynamics of the cytoskeleton and cell adhesion molecules, influencing cell movement and tissue organization.
• Survival signaling: C-src can promote cell survival by activating anti-apoptotic pathways, such as the PI3K/AKT pathway.

Regulation

C-src activity is tightly regulated by:

• Phosphorylation: The phosphorylation of Y527 by C-terminal Src kinase (Csk) inhibits c-src activity, while dephosphorylation by protein tyrosine phosphatases activates it.
• Protein interactions: Binding of the SH2 and SH3 domains to specific ligands can modulate c-src activity.
• Localization: C-src is targeted to specific cellular compartments, such as the plasma membrane, where it interacts with its substrates.

Clinical Significance

Dysregulation of c-src activity has been implicated in various diseases, particularly cancer. Overexpression or constitutive activation of c-src is associated with increased tumor growth, invasion, and metastasis. As a result, c-src is a potential target for cancer therapy, and several c-src inhibitors are being investigated in clinical trials.

Also see

• Tyrosine kinase
• Src family kinases
• Signal transduction
• Oncogene
• Protein phosphorylation