Preferred Label : SRC Tyrosine Kinase Activation Pathway;
NCIt related terms : Activation of Src by Protein-tyrosine phosphatase alpha;
Alternative definition : BIOCARTA: Progression through the cell cycle is accompanied by activation of the proto-oncogene
c-Src, a protein tyrosine kinase. Overexpression of Src leads to tyrosine phosphorylation
of multiple protein substrates and cellular transformation. During interphase the
Src protein folds back upon itself to stay in the inactive state, with a phosphotyrosine
residue in one domain at Tyrosine 529 bound by an SH2 domain in the same protein.
Activation of c-Src involves protein-tyrosine phosphatase alpha (PTP-alpha, or RPTP-alpha),
a transmembrane protein with a cytoplasmic phosphatase domain. A variety of evidence
has indicated that PTP-alpha dephosphorylates c-Src at Tyr529, allowing Src to open
up and become activated, and that this activation occurs in association with mitosis.
To activate Src, PTP-alpha must first open up the folded Src through binding itself
to the phosphorylated Src domain, a process blocked by binding of Grb-2 to PTP-alpha
at phosphorylated Tyr789. PTP-alpha phosphorylated at Tyr789 also binds to the Src
SH2 domain, causing the Src structure to open at Src Tyr529 to become available for
dephosphorylation. During mitosis the mitotic kinase Cdc-2 phosphorylates Src, along
with other cellular substrates, and in so doing makes Src more prone to PTP-alpha
dephosphorylation and activation. The activity of PTP-alpha toward Src is also regulated
by phosphorylation of PTP-alpha by protein kinase C at serines 180 and 204, releasing
the inhibition of PTP-alpha by Grb-2. In the normal cell cycle, Src activity is down-regulated
after cell division through dephosphorylation by protein phosphatases and phosphorylation
by Csk (C-terminal src kinase) and PTP-alpha dephosphorylation returns the cycle to
its interphase condition. The regulation of Src activity during mitosis demonstrates
how protein phosphorylation can shift the delicate equilibrium of molecular interactions
and cellular responses. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_srcRPTPPathway;
Origin ID : C39237;
UMLS CUI : C1519154;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
