Phosphorylation of unique domains of Src family kinases

Abstract

Members of the Src family of kinases (SFKs) are non-receptor tyrosine kinases involved in numerous signal transduction pathways. The catalytic, SH3 and SH2 domains are attached to the membrane-anchoring SH4 domain through the intrinsically disordered “Unique” domains, which exhibit strong sequence divergence among SFK members. In the last decade, structural and biochemical studies have begun to uncover the crucial role of the Unique domain in the regulation of SFK activity. This mini-review discusses what is known about the phosphorylation events taking place on the SFK Unique domains, and their biological relevance. The modulation by phosphorylation of biologically relevant inter- and intra- molecular interactions of Src, as well as the existence of complex phosphorylation/dephosphorylation patterns observed for the Unique domain of Src, reinforces the important functional role of the Unique domain in the regulation mechanisms of the Src kinases and, in a wider context, of intrinsically disordered regions in cellular processes.

EGF stimulates the activation of EGF receptors and the selective activation of major signaling pathways during mitosis

“…We also showed that EGF stimulated c-Src phosphorylation at Y418. Src plays diverse functions in cell signaling such as cell proliferation, differentiation, apoptosis, migration, and metabolism [54].…”

An Atlas of Phosphorylation and Proteolytic Processing Events During Excitotoxic Neuronal Death Reveals New Therapeutic Opportunities

“…The cleavage is expected to generate two truncated fragments: (i) a truncated Src fragment (ΔNSrc) containing the SH2, SH3 and kinase domains and the C-terminal tail and (ii) a short N-terminal fragment consisting of the SH4 domain and a large portion of the Unique region, which were previously found to adopt highly disordered conformations ( Figure 6E) (Arbesu et al, 2017;Perez et al, 2009). Since the SH4 domain and Unique region are critical to anchoring of Src to plasma membrane and intracellular vesicular membrane (Amata et al, 2014;Arbesu et al, 2017), most ΔNSrc resides in the cytosol of neurons (Hossain et al, 2013).…”

MicroRNA‐3064‐5p sponged by MALAT1 suppresses angiogenesis in human hepatocellular carcinoma by targeting the FOXA1/CD24/Src pathway

“…Therefore, the results presented above preliminarily suggest that miR-3064-5p has antiangiogenic effects and could function as a novel and promising prognostic predictor for HCC. 18 Therefore, the expression and activity of Src is critical for cell growth, proliferation, etc. Multiple studies have demonstrated that FOXA1 plays an oncogenic role and is expressed highly in several tumors, such as esophageal and lung cancer, thyroid cancer, prostate cancer, breast cancer, osteosarcoma, HCC, etc.…”