Gene Set: BIOCARTA_SRCRPTP_PATHWAY

Standard name BIOCARTA_SRCRPTP_PATHWAY
Systematic name M10994
Brief description Activation of Src by Protein-tyrosine phosphatase alpha
Full description or abstract 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 phophotyrosine 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 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 dephoshorylation returns the cycle to its interphase condition. The regulation of Src activity during mitosis demonstrates how protein phosphorylation can shifts the delicate equilibrium of molecular interactions and cellular responses.
Collection C2: curated gene sets
      CP: canonical pathways
            CP:BIOCARTA: BioCarta gene sets
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External links http://www.biocarta.com/pathfiles/h_srcRPTPPathway.asp
http://www.biocarta.com/pathfiles/PathwayProteinList.asp?showPFID=461
Organism Homo sapiens
Contributed by BioCarta
Source platform EntrezGeneIds
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Compute overlaps C1: positional gene sets
C2: curated gene sets
      CGP: chemical and genetic perturbations
      CP: canonical pathways
            CP:BIOCARTA: BioCarta gene sets
            CP:KEGG: KEGG gene sets
            CP:REACTOME: Reactome gene sets
C3: motif gene sets
      MIR: microRNA targets
      TFT: transcription factor targets
C4: computational gene sets
      CGN: cancer gene neighborhoods
      CM: cancer modules
C5: GO gene sets
      BP: GO biological process
      CC: GO cellular component
      MF: GO molecular function
Compendia expression profiles Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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