Phosphorylation of the SHC proteins on tyrosine correlates with the transformation of fibroblasts and erythroblasts by the v-sea tyrosine kinase.
The S13 avian erythroblastosis viral genome encodes an oncogenic tyrosine kinase, termed env-sea, that is capable of transforming fibroblasts and erythroblasts. Although the tyrosine kinase activity of the env-sea protein has been shown to be necessary for transformation, no substrates for this enzyme have been detected in vivo. Here we demonstrate that the recently described shc proteins are phosphorylated on tyrosine residues in both S13 transformed fibroblasts and erythroblasts. Furthermore, using an S13 temperature sensitive mutant, we show that the phosphorylation of the shc proteins occurs concomitantly with the activation of the tyrosine kinase activity of the env-sea protein. These observations make the phosphorylation of the shc proteins a good candidate for being involved in oncogenic signaling by the env-sea oncoprotein.
Crowe
A J
AJ
Department of Microbiology, State University of New York, Stony Brook 11794-5222.
McGlade
J
J
Pawson
T
T
Hayman
M J
MJ
D048868:Adaptor Proteins, Signal Transducing; D001355:Alpharetrovirus / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002472:Cell Transformation, Viral / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D004900:Erythroblasts / Q000382:microbiology*; D005347:Fibroblasts / Q000382:microbiology*; D051380:GRB2 Adaptor Protein; D020690:GTPase-Activating Proteins; D005786:Gene Expression Regulation / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013696:Temperature; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D020690:GTPase-Activating Proteins; C495950:Grb2 protein, rat; D009856:Oncogene Proteins, Viral; D011506:Proteins; C055694:env-sea oncogene protein, Avian Erythroblastosis Retrovirus; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D010738:Type C Phospholipases