Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways
The receptor for platelet-derived growth factor (PDGF) binds two proteins containing SH2 domains, GTPase activating protein (GAP) and phosphatidylinositol 3-kinase (Pl3-kinase). The sites on the receptor that mediate this interaction were identified by using phosphotyrosine-containing peptides repre...
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Veröffentlicht in: | Cell 1992-05, Vol.69 (3), p.413-423 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The receptor for platelet-derived growth factor (PDGF) binds two proteins containing SH2 domains, GTPase activating protein (GAP) and phosphatidylinositol 3-kinase (Pl3-kinase). The sites on the receptor that mediate this interaction were identified by using phosphotyrosine-containing peptides representing receptor sequences to block specifically binding of either Pl3-kinase or GAP. These results suggested that Pl3-kinase binds two phosphotyrosine residues, each located in a 5 aa motif with an essential methionine at the fourth position C-terminal to the tyrosine. Point mutations at these sites caused a selective elimination of Pl3-kinase binding and loss of PDGF-stimulated DNA synthesis. Mutation of the binding site for GAP prevented the receptor from associating with or phosphorylating GAP, but had no effect on Pl3-kinase binding and little effect on DNA synthesis. Therefore, GAP and Pl3-kinase interact with the receptor by binding to different phosphotyrosine-containing sequence motifs. |
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ISSN: | 0092-8674 1097-4172 |
DOI: | 10.1016/0092-8674(92)90444-H |