Src protein kinase is activated in many human tumor cells and plays an important role in tumorigenesis and development. The regulation of Src activity mainly includes covalent modification and isoform regulation, but gene mutation and other methods can also regulate its activity. The covalent modification Src is mainly phosphorylation, and Tyr530, Tyr419, Thr34, Thr46, Ser72, Tyr138 and Tyr213 are all phosphorylation sites of Src, and Tyr530 and Tyr419 are the most important phosphorylation sites of Src. Isomerization regulation includes regulation of binding of SH3, SH2, etc., involving focal adhesion kinase (FAK), progesterone receptor (PR), estrogen receptor (ER), and male androgen receptor (AR), P130Cas, platelet-derived growth factor (PDGF), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor, human epidermal growth factor receptor-2 (ERBB2/HER2/NEU), insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor receptor (FGFR1), hepatocyte growth factor receptor (hepatocyte growth factor receptor) c-Met), an accessory protein p13 encoded by human type 1 T cell leukemia virus, HIV-1 virulence factors Nef and Sin.
The Src kinase family
The Src kinase family is a protein with tyrosine protein kinase activity that includes nine members: Src, Blk, Fgr, Fyn, Hck, Lyn, Lck, Yes, and Yrk. From N-terminus to C-terminus, Src It consists of SH4 domain, specific fragment, SH3 domain, SH2 domain, junction segment, SH1 domain (protein tyrosine kinase domain) and carboxy terminal regulatory tail. There is Src at the N-terminus of Src. A region localized on the cell membrane, which is generally palmitoylated or myristoylated. As a prototype, chicken Src kinase consists of 533 amino acids, while human Src kinase consists of 536 amino acids. Different from chicken Src protein kinase, three amino acids have been inserted into human Src specific fragments. Studies have shown that Src plays an important role in cell processes such as cell proliferation, differentiation, movement and localization. The Src gene product c-Src is overexpressed and highly activated in a variety of human tumor cells, and activation of src activates the MAPK and PI3K/Akt pathways involved in tumor progression.
Regulation of Src kinase
Src kinase activity can be controlled by a variety of regulatory mechanisms. A large number of studies have now explained Src, etc., covalent modification, heterogeneous regulation is the most important regulatory mechanism found. In covalent regulation, phosphorylation regulation has been It is the research focus of Src kinase regulation mechanism, especially the phosphorylation of Tyr530 and Tyr419 sites of Src and the regulation of these two sites by some protein tyrosine phosphatase and tyrosine kinase. Phosphorylation of the Tyr530 and Tyr419 sites of Src plays a major role in the regulation of Src activity. However, we found that phosphorylation of the Src Tyr530 site does play an important role in the regulation of Src activity, on the other hand, Src Phosphorylation at Tyr419 does not always reflect the level of Src activity. We found that phosphorylation at Tyr530 site is dominant in Src regulation, and Src phosphorylation at Tyr419 site may be an indicator of increased Src activity. However, due to the phosphorylation of Tyr530 site, Src activity was dominantly decreased and Tyr419 site was not dephosphorylated in time. Therefore, phosphorylation of Tyr419 site could not reflect the level of Src activity. Src was fine in tumor. The regulatory mechanism in the past is unknown, and scientists found that PTP1B plays an important role in it. In addition, in some unique tumor cells, such as colon cancer cells, CHK molecules may play an important role in Src regulation and may not be limited to colon cancer.
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