Gene interactions and pathways from curated databases and text-mining
Oncogene 2000, PMID: 10918571

Shp-2 mediates v-Src-induced morphological changes and activation of the anti-apoptotic protein kinase Akt.

Hakak, Y; Hsu, Y S; Martin, G S

The protein-tyrosine phosphatase Shp-2 is a positive modulator of the Ras/mitogen-activated protein kinase pathway and a putative substrate of the transforming non-receptor tyrosine kinase v-Src. To characterize the role of Shp-2 in cellular transformation and signaling by v-Src, we expressed v-Src in normal and Shp-2-deficient mouse embryo fibroblasts. Expression of Shp-2 was found to be necessary for morphological transformation by v-Src: Shp-2+/+ cells became rounded or spindly upon v-Src expression, whereas Shp-2-deficient cells remained relatively flat. v-Src-induced reorganization of the actin cytoskeleton and the formation of podosomes were compromised in Shp-2-deficient cells. Shp-2 deficiency also reduced v-Src-induced activation of the anti-apoptotic protein kinase Akt. The reduced activation of Akt in Shp-2-deficient cells correlated with a reduction in the association of the p85 regulatory subunit of PI3-kinase with the adapter protein Cbl. Activation of PI3-kinase by v-Src may be mediated by the association of the adapter protein Cbl with the p85 subunit. Since activation of Akt is dependent on PI3-kinase, this suggests that the effect of Shp-2 on Akt activation may be mediated, at least in part, by its effects on the interaction between PI3-kinase and Cbl. The defect in activation of the Akt survival pathway also correlated with enhanced sensitivity of Shp-2-deficient cells to an apoptosis-inducing agent. These results implicate Shp-2 in v-Src-induced cytoskeletal reorganization and activation of the Akt cell survival pathway.

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Text Mining Data

Akt → v-Src: " Shp-2 mediates v-Src induced morphological changes and activation of the anti-apoptotic protein kinase Akt "

Akt → Shp-2: " Shp-2 mediates v-Src induced morphological changes and activation of the anti-apoptotic protein kinase Akt "

Akt → v-Src: " Shp-2 deficiency also reduced v-Src induced activation of the anti-apoptotic protein kinase Akt "

Akt → Shp-2: " Shp-2 deficiency also reduced v-Src induced activation of the anti-apoptotic protein kinase Akt "

v-Src → p85: " Activation of PI3-kinase by v-Src may be mediated by the association of the adapter protein Cbl with the p85 subunit "

v-Src → Cbl: " Activation of PI3-kinase by v-Src may be mediated by the association of the adapter protein Cbl with the p85 subunit "

v-Src → PI3-kinase: " Activation of PI3-kinase by v-Src may be mediated by the association of the adapter protein Cbl with the p85 subunit "

PI3-kinase → p85: " Activation of PI3-kinase by v-Src may be mediated by the association of the adapter protein Cbl with the p85 subunit "

PI3-kinase → Cbl: " Activation of PI3-kinase by v-Src may be mediated by the association of the adapter protein Cbl with the p85 subunit "

Cbl ⊣ Shp-2: " Since activation of Akt is dependent on PI3-kinase, this suggests that the effect of Shp-2 on Akt activation may be mediated , at least in part, by its effects on the interaction between PI3-kinase and Cbl "

PI3-kinase ⊣ Shp-2: " Since activation of Akt is dependent on PI3-kinase, this suggests that the effect of Shp-2 on Akt activation may be mediated , at least in part, by its effects on the interaction between PI3-kinase and Cbl "

Akt → Cbl: " Since activation of Akt is dependent on PI3-kinase, this suggests that the effect of Shp-2 on Akt activation may be mediated , at least in part, by its effects on the interaction between PI3-kinase and Cbl "

Akt → PI3-kinase: " Since activation of Akt is dependent on PI3-kinase , this suggests that the effect of Shp-2 on Akt activation may be mediated, at least in part, by its effects on the interaction between PI3-kinase and Cbl "

Akt — Shp-2: " Since activation of Akt is dependent on PI3-kinase, this suggests that the effect of Shp-2 on Akt activation may be mediated, at least in part, by its effects on the interaction between PI3-kinase and Cbl "

Manually curated Databases

  • IRef Biogrid Interaction: CBL — PIK3R1 (direct interaction, pull down)
  • IRef Biogrid Interaction: CBL — PIK3R1 (physical association, affinity chromatography technology)
In total, 1 gene pairs are associated to this article in curated databases