| 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 |
| Source publication |
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| Exact source |
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| Related 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 |
| Dataset references |
|
| Download gene set |
format: grp | text | gmt | gmx | xml |
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
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Compendia expression profiles  |
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
|
| Advanced query |
Further investigate
these 11 genes |
Gene families  |
Categorize these
11 genes by gene family |
| Show members |
(show 11 members mapped to 11 genes)
Original Member |
Gene Symbol |
Gene Description |
Entrez Gene Id |
| 1445 |
CSK |
c-src tyrosine kinase |
1445 |
| 2885 |
GRB2 |
growth factor receptor-bound protein 2 |
2885 |
| 5578 |
PRKCA |
protein kinase C, alpha |
5578 |
| 5579 |
PRKCB |
|
5579 |
| 5786 |
PTPRA |
protein tyrosine phosphatase, receptor type, A |
5786 |
| 6714 |
SRC |
v-src sarcoma (Schmidt-Ruppin A-2) viral oncogen... |
6714 |
| 891 |
CCNB1 |
cyclin B1 |
891 |
| 983 |
CDK1 |
|
983 |
| 993 |
CDC25A |
cell division cycle 25A |
993 |
| 994 |
CDC25B |
cell division cycle 25B |
994 |
| 995 |
CDC25C |
cell division cycle 25C |
995 |
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| Version history |
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