CrkII signals from epidermal growth factor receptor to Ras.
A rat fibroblast mutant defective in oncogenic transformation and signaling from epidermal growth factor receptor to Ras has been isolated. The mutant contains dominant negative-type point mutations in the C-terminal SH3 domain of one crkII gene. Among the adapters tested, the mutant is complemented only by crkII cDNA. Expression of the mutated crkII in parent cells generates the phenotype indistinguishable from the mutant cell. Yet overexpression or reduced expression of Grb2 in the mutant before and after complementation with crkII have little effect on its phenotype. We conclude that adapter molecules are highly specific and that the oncogenic growth signal from epidermal growth factor receptor to Ras is predominantly mediated by CrkII in rat fibroblast.
Okayama Cell Switching Project, Research Development Corporation of Japan, Kyoto, Japan.
S
S
Kizaka-Kondoh
M
M
Matsuda
H
H
Okayama
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D047390:Casein Kinase II; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D018631:ras Proteins