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Tyrosyl phosphorylation and growth factor receptor association of the human corkscrew homologue, SH-PTP2
R J Lechleider1, R M Freeman, B G Neel
1Molecular Medicine Unit, Beth Israel Hospital, Boston, Massachusetts 02215.
Abstract:
The pivotal role of tyrosine kinases in signal transduction is well established, but the role of tyrosine phosphatases remains obscure. The discovery of src homology 2 domain-containing protein tyrosine phosphatases suggested roles for these molecules in growth factor signaling pathways, since src homology 2 domains direct association of downstream signaling molecules with activated growth factor receptors and other phosphotyrosyl proteins. We have found that SH-PTP2, a putative homologue of Drosophila corkscrew, associates in vivo with the ligand-activated epidermal growth factor and platelet-derived growth factor receptors. The N-terminal src homology 2 domain of SH-PTP2 directly associates with activated receptors. SH-PTP2 itself is a phosphoprotein, and it becomes tyrosyl phosphorylated upon growth factor activation. These findings suggest several possible models for SH-PTP2 signaling.
Insights
Src homology 2 domain-containing protein tyrosine phosphatase 2 (SH-PTP2) associates with growth factor receptors, suggesting its role in cell signaling pathways. This protein tyrosine phosphatase becomes phosphorylated upon growth factor activation.
Area of Science:
- Molecular Biology
- Cell Signaling
- Biochemistry
Background:
- The function of tyrosine phosphatases in signal transduction is not well understood.
- Src homology 2 (SH2) domain-containing protein tyrosine phosphatases are implicated in growth factor signaling.
- SH2 domains mediate interactions between signaling molecules and activated receptors.
Purpose of the Study:
- To investigate the role of SH-PTP2 in growth factor signaling pathways.
- To determine the interaction of SH-PTP2 with activated growth factor receptors.
- To explore the phosphorylation status of SH-PTP2 upon growth factor stimulation.
Main Methods:
- In vivo association studies using ligand-activated growth factor receptors.
- Analysis of SH-PTP2 N-terminal SH2 domain interactions.
- Assessment of SH-PTP2 phosphorylation following growth factor activation.
Main Results:
- SH-PTP2 associates in vivo with activated epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors.
- The N-terminal SH2 domain of SH-PTP2 directly binds to activated receptors.
- SH-PTP2 is a phosphoprotein that undergoes tyrosyl phosphorylation upon growth factor stimulation.
Conclusions:
- SH-PTP2 plays a role in growth factor receptor-mediated signal transduction.
- The interaction of SH-PTP2 with activated receptors is mediated by its SH2 domain.
- Growth factor activation leads to the phosphorylation of SH-PTP2, suggesting its involvement in signaling cascades.