Overexpression of Shc proteins potentiates the proliferative response to the granulocyte-macrophage colony-stimulating factor and recruitment of Grb2/SoS and Grb2/p140 complexes to the beta receptor subunit.

摘要: The high affinity receptor for GM-CSF consists of a unique alpha subunit and beta that is shared with receptors IL-3 IL-5. Activation (GMR) triggers two distinct cytoplasmic signalling pathways, JAK2 Ras, sufficient to maintain proliferation growth factor-dependent cell lines. Shc proteins are phosphorylated upon activation GMR may be involved in the transmission signals Ras. To define role cells stimulated GM-CSF, we investigated both network interactions involve after stimulation effects overexpressing on proliferative response GM-CSF. Two complexes, Grb2/Sos Grb2/p140 bind through Grb2 SH2 domain Shc, thereby recruited subunit. Both complexes stable, even absence ligand, depend direct association p140 Sos respectively SH3 domains Grb2. an uncharacterized protein constitutively tyrosine and, its Grb2-bound form, expressed only hematopoietic cells, oligomeric complex formed by subunit-phosphorylated Shc-Grb2-SoS-p140 also induced L-5 growth-factor dependent Overexpression wild-type increases MAP kinase These require Taken together these results indicate phosphorylation crucial step stimuli, since it creates binding site Grb2/SoS complex, whose function activate Ras remains unknown.