Proto-oncogene tyrosine-protein kinase Src

The tyrosine kinase Src ( c -Src also: composite acronym of cellular and sarcoma ) is an endogenous protein of the family of tyrosine kinases, which is present in the cytosol of the cell. c -Src is the gene product of the same proto-oncogene SRC, ie a precursor of a potentially cancer-causing gene and is considered the best-studied proto-oncogene at all. c -Src was discovered in the 1970s by J. Michael Bishop, Harold E. Varmus and coworkers as the cell's own homolog of the oncogene v -Src of Rous sarcoma virus. Thus, they provided important insights into the development of cancer by misguided endogenous trigger for which she received in 1989 the Nobel Prize in Physiology or Medicine. c -Src was also the first member of the tyrosine kinase could be identified.

C -Src is also the prototype of the kinases of the Src family which also includes Lyn, Fyn, Lck, Hck, Fgr, Blk, YRK and c -Yes.



C -Src is a cytosolic protein present associated with the cell membrane, and is encoded by a gene on chromosome 20 q12 - q13 locus. c -Src consists of four so-called Src homology domains (SH1 -4). The SH1 domain carries, both essential for the autophosphorylation and thus for the function of c- Src tyrosine groups as well as the kinase function. SH2 and SH3 domains contain binding sites for a phosphotyrosine residue or a Polyprolinstruktur SH1 domain located close to the contained in the C-terminus of c -Src. SH2 and SH3 are responsible for the regulation of c- Src, together with the C-terminus. The SH4 domain contains myristoylation and is thus responsible for anchoring in the cell membrane. The first sequence of src in 1980 by Armin P. Czernilofsky et al. published and the tyrosine phosphorylation of v -src and c -src in 1981 by JE Smart and A. P. Czernilofsky et al. determined.

Activation and regulation

The activity of c -Src is regulated primarily via phosphorylation and dephosphorylation of the tyrosine residue in the C -terminus ( Y530 ). Tyrosine phosphorylation of this leads to a binding of the SH2 domain to the C- terminus, and to a secondary connection of the SH3 bearing SH1 kinase domain. By linking SH1 to SH3, the kinase function is inhibited by which c -Src is present in an inactive state. Since the viral v -Src, the C -terminus including the essential for the inactivation tyrosine residue is missing, this is a permanently active ( constitutively active ) prior condition.

The protein kinases Csk and Chk lead via phosphorylation of the C -terminal tyrosine to inactivation of c- Src. The opposite can be activated via dephosphorylation of these tyrosine protein tyrosine phosphatases c -Src. In addition, c -Src independent of phosphorylation by competitive binding of interaction partners, such as Fak and Cas, to the phosphotyrosine - binding site of the SH2 domain or the polyproline binding site of the SH3 domain to be activated. This mechanism also activated receptor tyrosine kinases c -Src can activate.


C -Src is a protein kinase that can activate a number of other proteins. The substrates of c- Src include, in particular focal adhesion proteins, adapter proteins and transcription factors. As important signaling molecules, such as Fak, Cas, Fish, cortactin, p120 catenin, RhoGAP, RRAS, JNK and STAT3, are directly or indirectly activated by c- Src, takes c -Src play a key role in the intracellular signal transduction one.