Abstract
A cDNA clone encoding a novel, widely expressed protein (called growth factor receptor-bound protein 2 or GRB2) containing one src homology 2 (SH2) domain and two SH3 domains was isolated. Immunoblotting experiments indicate that GRB2 associates with tyrosine-phosphorylated epidermal growth factor receptors (EGFRs) and platelet-derived growth factor receptors (PDGFRs) via its SH2 domain. Interestingly, GRB2 exhibits striking structural and functional homology to the C. elegans protein sem-5. It has been shown that sem-5 and two other genes called let-23 (EGFR like) and let-60 (ras like) lie along the same signal transduction pathway controlling C. elegans vulval induction. To examine whether GRB2 is also a component of ras signaling in mammalian cells, microinjection studies were performed. While injection of GRB2 or H-ras proteins alone into quiescent rat fibroblasts did not have mitogenic effect, microinjection of GRB2 together with H-ras protein stimulated DNA synthesis. These results suggest that GRB2/sem-5 plays a crucial role in a highly conserved mechanism for growth factor control of ras signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Base Sequence
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Blotting, Northern
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Blotting, Western
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Caenorhabditis / genetics
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Cell Line
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DNA / biosynthesis
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DNA / isolation & purification
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ErbB Receptors / metabolism*
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GRB2 Adaptor Protein
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Humans
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Mice
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Microinjections
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Molecular Sequence Data
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Oncogene Protein p21(ras) / metabolism*
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Phosphorylation
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Platelet-Derived Growth Factor / metabolism
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Protein-Tyrosine Kinases / metabolism*
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Proteins / chemistry
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Proteins / genetics*
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Proteins / metabolism
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Receptors, Cell Surface / metabolism*
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Receptors, Platelet-Derived Growth Factor
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Sequence Alignment
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Signal Transduction*
Substances
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Adaptor Proteins, Signal Transducing
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GRB2 Adaptor Protein
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GRB2 protein, human
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Grb2 protein, mouse
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Platelet-Derived Growth Factor
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Proteins
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Receptors, Cell Surface
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DNA
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ErbB Receptors
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Protein-Tyrosine Kinases
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Receptors, Platelet-Derived Growth Factor
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Oncogene Protein p21(ras)
Associated data
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GENBANK/L05499
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GENBANK/M87278
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GENBANK/M94130
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GENBANK/M94264
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GENBANK/M96995
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GENBANK/S72766
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GENBANK/S72767
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GENBANK/S72768
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GENBANK/S72769
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GENBANK/S72771