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Direct interaction between Shc and the platelet-derived growth factor beta-receptor
The Src homology 2 (SH2) domain-containing Shc proteins p52shc and p46shc become phosphorylated upon activation of several tyrosine kinases and are implicated in mitogenic signal transduction. Ligand stimulation of the platelet-derived growth factor (PDGF) beta-receptor leads to autophosphorylation...
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Published in: | The Journal of biological chemistry 1994-05, Vol.269 (21), p.15337-15343 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The Src homology 2 (SH2) domain-containing Shc proteins p52shc and p46shc become phosphorylated upon activation of several
tyrosine kinases and are implicated in mitogenic signal transduction. Ligand stimulation of the platelet-derived growth factor
(PDGF) beta-receptor leads to autophosphorylation of tyrosine residues, which is known to mediate interactions with several
SH2 domain-containing signaling molecules. In this study, we have characterized the interaction between the PDGF beta-receptor
and Shc. PDGF beta-receptor coprecipitation in Shc immunoprecipitates was dependent on stimulation with PDGF-BB. The Shc SH2
domain expressed as a bacterial fusion protein bound the autophosphorylated PDGF beta-receptor. Moreover, the Shc SH2 domain
could bind the autophosphorylated purified baculovirus-expressed PDGF beta-receptor intracellular domain, which indicates
a direct association of Shc with the PDGF beta-receptor. Activation of the PDGF beta-receptor induced the preferential phosphorylation
of p52shc. Tyrosine-phosphorylated Shc, in turn, formed a complex with the signaling molecule Grb2. Synthetic peptide analysis
revealed that certain autophosphorylation sites in the PDGF beta-receptor (Tyr-579, Tyr-740, Tyr-751, and Tyr-771) were able
to mediate the specific binding of the Shc SH2 domain as well as intact Shc proteins. A mutant PDGF beta-receptor in which
Tyr-579 was replaced with phenylalanine showed 40% impaired association of Shc in vivo, but phosphorylation of Shc proteins
was not affected. We conclude that multiple autophosphorylation sites in the PDGF beta-receptor are responsible for the binding
of Shc. This is in contrast to previously characterized interactions between the PDGF beta-receptor and SH2 domain-containing
proteins, which generally involve one high affinity binding site in the receptor. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/s0021-9258(17)36611-5 |