Tyrosine phosphorylation of a 94-kDa protein associated with GRB2/ASH is implicated in the signal transduction of hematopoietic survival factors.
Grb2/Ash is an adapter molecule that contains Src-homology (SH) 2 and 3 domains. We have examined Grb2/Ash-associated proteins in hematopoietic cells, and have noted a 94-kDa phosphotyrosine-containing protein (pp94) among them. It was shown that the SH2 domain of Grb2/Ash is necessary for the binding of pp94 to Grb2/Ash from the binding experiments using the GST Fusion proteins and the phosphotyrosine analogue phenylphosphate. Tyrosine phosphorylation of pp94 was rapid and transient, and was only observed when the cells were stimulated with factors that were absolutely required for survival of the cells (survival factors). The kinase inhibitors, staurosporine and genistein, inhibit the proliferation UT-7 cells. However, genistein does not inhibit the survival of the cells while staurosporine inhibits both the proliferation and the survival of the cells. Tyrosine phosphorylation of pp94 was sensitive to staurosporine but resistant to genistein. It is possible that tyrosine phosphorylation of pp94 might be related to the survival rather than to the proliferation of the cells.
Hanazono
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Sasaki
K
K
Odai
H
H
Yazaki
Y
Y
Hirai
H
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D066246:ErbB Receptors / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010755:Organophosphates / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D010755:Organophosphates; D011506:Proteins; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; C074782:phenylphosphate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D066246:ErbB Receptors