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Biosynthesis-P60c-src
Definition
The cellular proto-oncogene p60c-src (src) is a cytosolic nonreceptor tyrosine kinase.
Discovery
In 1911, Peyton Rous reported that a fibrosarcoma can be transmitted between chickens in a cell-free extract tumor1. The transfer agent, the Rous sarcoma virus (RSV) transformed cells under the presence in the genome of a viral oncogene, v-src, which is derived from a normal cellular gene that has been collected, or transduced by the virus. The cellular proto-oncogene, c-Src, encodes a protein p60c-src, which has the ability to phosphorylate proteins on tyrosine residues. RSV studies were therefore directly responsible for the discovery of cellular proto-oncogenes and protein tyrosine kinases, discoveries that have been instrumental in the formation of ideas on cell growth control2.
Features structural
The c-src gene family has nine known members (black, c-FGR, Fyn, HCK, lck, lyn, c-src, c-yes and yrk), each encoded a cytoplasmic protein-tyrosine kinase (PTK) appears to be involved in signal transduction. The c-src PTKs contain three domains (SH1, SH2 and SH3) that are in many signaling proteins. The SH1 domain has PTK activity, whereas the SH2 and SH3 domains are involved in mediating protein-protein interactions phosphotyrosine binding containing and proline-rich motifs, respectively3.
Mode of Action
A study showed that, compared with the DNA sequence of the virus from the parents of c-src, transforming the two src mutant virus containing a single point mutations that result a single amino acid changes in the src gene product (protein P60). The two amino acid changes reside in the domain of the protein tyrosine kinase. The mutation a virus is detected in the normal replacement of Glu-378 in p60c-src by Gly, while the P60 virus transformation of others has phenylalanine in place of normal Ile-441. This indicates that when p60c-src is expressed at high levels in a retroviral context, a single amino acid change in its primary sequence can trigger activity protein kinase, causing cell transformation4.
Features
p60c-src function in a wide range of situations biological, which regulate the behavior of terminally differentiated, post mitotic cell types. Targeted disruption of family members c-Src in transgenic mice has confirmed an important role in T cell maturation and activation. p60c-src plays an important role in maintaining bone, learning, memory and signal transduction mediating cell growth, transformation of differentiation, and tissue remodeling in different organs5.
References:
1. Rous P (1911). A bird sarcoma transmissible agent separated from the cells tumor. J. Exp Med, 13 (4) :397-411.
2. Brickell PM (1992). P60c-src family of protein tyrosine kinases: structure, regulation and function Crit .. Revelation oncogenes., 3 (4) :401-446.
3. Kefalas P, Brown TR, Brickell PM (1995). Signalling by the p60c-src family protein tyrosine kinases. Int J Biochem Cell Biol, 27 (6) :551-563.
4. Levy JB, Iba H, Hanafusa H (1986). Activation potential transforming p60c-src by an amino acid change. PNAS., 83 (12) :4228-4232.
5. Kefalas P, Brown TR, Brickell PM (1995). Family signaling p60c-src protein-tyrosine kinases. Int J Biochem Cell Biol . , 27 (6) :551-563.
About the Author
P60c-src also plays an important role in bone maintenance, learning, memory and signal transduction which mediate cell growth, differentiation, transformation and tissue remodeling in various organs.
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