Growth Factors Stimulate Tyrosine Dephosphorylation of p75 and Its Dissociation from the SH2 Domain of Grb2

Yoon Pin Lim, Boon Chuan Low, Siew Hwa Ong, Graeme R. Guy
1997 Journal of Biological Chemistry  
The growth factor receptor-binding protein (Grb2) has a key role in initiating the mitogen-activated protein kinase signaling cascade in major cell regulatory pathways. The binding of proteins to the SH2 domain of Grb2 has been reported to occur mainly after they are tyrosine-phosphorylated following receptor activation. Using an in vitro binding assay, immunoprecipitation, and Far Western techniques, we report that in quiescent cells a 75-kDa protein binds directly to the SH2 domain of Grb2.
more » ... l of the tyrosine-phosphorylated p75 protein co-localizes with Grb2⅐Sos complex in the cytosolic fraction of the cell in vivo and undergoes tyrosine dephosphorylation when cells are treated with mitogenic ligands such as epidermal, platelet-derived, and fibroblast growth factors, endothelin-1, and bombesin but not tumor necrosis factor-␣, interferon-␣ and -␥, interleukein-6, and leukemic inhibitory factor, which are either cell growth inhibitory or not significantly mitogenic. The dephosphorylation of p75 and the ensuing dissociation from Grb2 is rapid, occurring within 30 s following mitogenic stimulation by ligands such as epidermal growth factor, suggesting p75 to be an early component in the signal transduction pathways involving Grb2.
doi:10.1074/jbc.272.47.29892 pmid:9368064 fatcat:gvxnser6kjgwlhj7hg52hifmkm