SHP1 and SHP2 protein-tyrosine phosphatases associate with beta c after interleukin-3-induced receptor tyrosine phosphorylation. Identification of potential binding sites and substrates

• Published in: The Journal of biological chemistry 1997-05, Vol.272 (22), p.14470-14476
• Main Authors: Bone, H, Dechert, U, Jirik, F, Schrader, J W, Welham, MJ
• Format: Article
• Language: English
• ISSN: 0021-9258
• DOI: 10.1074/jbc.272.22.14470

The cytoplasmic tyrosine phosphatases, SHP1 and SHP2, are implicated in the control of cellular proliferation and survival. Here we demonstrate that both SHP1 and SHP2 associate with the beta c subunit of the human interleukin-3 (IL-3) receptor following IL-3 stimulation and that the src homology region 2 (SH2) domains of these phosphatases mediate this interaction. Sequential immunoprecipitation analyses suggest this interaction is direct. Competition studies, using phosphotyrosine-containing peptides based on sequences surrounding key tyrosine residues within beta c, suggest that phosphorylation of tyrosine 612 is the key event mediating the association of beta c with SHP1 and SHP2. However, inhibition of SHP2 binding to beta c, did not prevent tyrosine phosphorylation of SHP2. Interestingly, this same phosphopeptide served as a substrate for the tyrosine phosphatase activity of both SHP1 and SHP2. Binding of these protein-tyrosine phosphatases to the IL-3 receptor may regulate IL-3 signal transduction pathways, both through their catalytic activity and through the recruitment of other molecules to the receptor complex.