Finding
These results suggest that the SH2 domain of SH2-Bβ is necessary and sufficient to mediate the interaction between SH2-Bβ and PDGFR.
Paper
Platelet-derived Growth Factor (PDGF) Stimulates the Association of SH2-Bβ with PDGF Receptor and Phosphorylation of SH2-Bβ*
Abstract
We recently identified SH2-Bβ as a JAK2-binding protein and substrate involved in the signaling of receptors for growth hormone and interferon-γ. In this work, we report that SH2-Bβ also functions as a signaling molecule for platelet-derived growth factor (PDGF). SH2-Bβ fused to glutathione S-transferase (GST) bound PDGF receptor (PDGFR) from PDGF-treated but not control cells. GST fusion protein containing only the SH2 domain of SH2-Bβ also bound PDGFR from PDGF-treated cells. An Arg to Glu mutation within the FLVRQS motif in the SH2 domain of SH2-Bβ inhibited GST-SH2-Bβ binding to tyrosyl-phosphorylated PDGFR. The N-terminal truncated SH2-Bβ containing the entire SH2 domain interacted directly with tyrosyl-phosphorylated PDGFR from PDGF-treated cells but not unphosphorylated PDGFR from control cells in a Far Western assay. These results suggest that the SH2 domain of SH2-Bβ is necessary and sufficient to mediate the interaction between SH2-Bβ and PDGFR. PDGF stimulated coimmunoprecipitation of endogenous SH2-Bβ with endogenous PDGFR in both 3T3-F442A and NIH3T3 cells. PDGF stimulated the rapid and transient phosphorylation of SH2-Bβ on tyrosines and most likely on serines and/or threonines. Similarly, epidermal growth factor stimulated the phosphorylation of SH2-Bβ; however, phosphorylation appears to be predominantly on serines and/or threonines. In response to PDGF, SH2-Bβ associated with multiple tyrosyl-phosphorylated proteins, at least one of which (designated p84) does not bind to PDGFR. Taken together, these data strongly argue that, in response to PDGF, SH2-Bβ directly interacts with PDGFR and is phosphorylated on tyrosine and most likely on serines and/or threonines, and acts as a signaling protein for PDGFR.
Authors
L. Rui, C. Carter-Su
Journal
The Journal of Biological Chemistry