The Grb2 binding domain of mSos1 is not required for downstream signal transduction.
Cellular Ras proteins are activated primarily by specific guanine-nucleotide releasing factors such as the Son of Sevenless (Sos) proteins. This activation event is thought to occur in response to plasma membrane localization of a complex containing Sos and a small adapter protein Grb2. We have isolated a dominant mutant allele of mSos1 which transforms Rat1 cells, yet is no longer able to bind Grb2. Biochemical experiments reveal that the subcellular distribution of this truncated Sos protein is not altered with respect to the wild type Sos protein. These data argue against a role for Grb2 in the direct recruitment of Sos proteins to the plasma membrane and suggest that Grb2 may function to overcome negative regulation of Sos by its C terminus.
Wang
W
W
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Fisher
E M
EM
Jia
Q
Q
Dunn
J M
JM
Porfiri
E
E
Downward
J
J
Egan
S E
SE
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000235:genetics; D016368:Frameshift Mutation; D051380:GRB2 Adaptor Protein; D020662:Guanine Nucleotide Exchange Factors; D008954:Models, Biological; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014170:Transformation, Genetic; D020663:ras Guanine Nucleotide Exchange Factors
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D004247:DNA