Proto-oncogene tyrosine-protein kinase Src

Proto-oncogene tyrosine-protein kinase Src, also known as Src, is a non-receptor tyrosine kinase that is critical in the regulation of various cellular processes, including cell division, survival, migration, and angiogenesis. Src belongs to the Src family kinases (SFKs), which are implicated in the control of cell adhesion, growth, and differentiation. The Src gene was originally identified as the cellular counterpart of the v-Src oncogene of the Rous sarcoma virus, the first retrovirus shown to cause cancer in chickens. This discovery was pivotal in the field of cancer research, highlighting the role of cellular oncogenes in the development of cancer.

Function

Src plays a multifaceted role in cellular physiology. It is involved in signaling pathways that regulate the cytoskeleton, thereby affecting cell shape and movement. Src kinase activity is also essential for the proper regulation of cell cycle progression and apoptosis. In addition, Src has been found to interact with receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), to propagate intracellular signals that promote cell proliferation and survival.

Regulation

The activity of Src is tightly regulated by its structure and by phosphorylation. In its inactive state, Src adopts a closed conformation through the interaction of its SH2 domain with a phosphorylated tyrosine residue at its C-terminal tail. Phosphorylation of this tyrosine residue (Tyr527 in chicken and Tyr530 in humans) by another kinase, C-terminal Src kinase (Csk), helps maintain Src in its inactive state. Activation of Src involves dephosphorylation of this tyrosine residue, leading to an open conformation that is catalytically active.

Role in Cancer

The deregulation of Src activity has been implicated in the progression of various cancers. Overexpression or constitutive activation of Src has been observed in colon, breast, prostate, and pancreatic cancers, among others. Src contributes to oncogenic processes by promoting cell proliferation, survival, invasion, and metastasis. Given its central role in cancer biology, Src has become a target for therapeutic intervention. Several Src inhibitors have been developed and are currently being tested in clinical trials for their efficacy in treating cancer.

Src Inhibitors

Src inhibitors are small molecules designed to selectively inhibit the kinase activity of Src. These inhibitors have shown promise in preclinical studies, demonstrating the ability to reduce tumor growth, invasion, and metastasis. However, the clinical efficacy of Src inhibitors in cancer therapy remains under investigation, with challenges such as drug resistance and toxicity.

Conclusion

Proto-oncogene tyrosine-protein kinase Src is a crucial player in the regulation of cell behavior, with significant implications for cancer development and therapy. Ongoing research aims to further elucidate the complex roles of Src in cancer and to optimize Src-targeted therapies for clinical use.