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PMID:8596638

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Citation

Holgado-Madruga, M, Emlet, DR, Moscatello, DK, Godwin, AK and Wong, AJ (1996) A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature 379:560-4

Abstract

The protein Grb2 plays a central role in signalling by receptor protein-tyrosine kinases, where its SH2 domain binds to the receptor and its two SH3 domains link to effectors. One target effector is Sos, so Grb2 links receptor protein-tyrosine kinases with the Ras signalling pathway. The SH3 domains can also couple to other signalling proteins, including Vav, c-Abl and dynamin. We have identified several bands in glial and medulloblastoma tumours that are recognized by Grb2 but these did not correspond to any known protein. Here we use recombinant Grb2 to isolate a complementary DNA called Gab1 (for Grb2-associated binder-1). Gab1 shares amino-acid homology and several structural features with IRS-1 (insulin-receptor substrate-1; refs 6,7), is a substrate of the EGF and insulin receptors, and can act as a docking protein for several SH2-containing proteins. Over-expression of Gab1 enhances cell growth and results in transformation. We conclude that Gab1 is a new protein in EGF and insulin receptor signalling which could integrate signals from different systems.

Links

PubMed Online version:10.1038/379560a0

Keywords

3T3 Cells; Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Blotting, Northern; Blotting, Western; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Cell Division; Cell Transformation, Neoplastic; DNA, Complementary; Enzyme Activation; GRB2 Adaptor Protein; Humans; Mice; Molecular Sequence Data; Phosphatidylinositol 3-Kinases; Phosphoproteins/genetics; Phosphoproteins/metabolism; Phosphotransferases (Alcohol Group Acceptor)/metabolism; Proteins/metabolism; Receptor, Epidermal Growth Factor/metabolism; Receptor, Insulin/metabolism; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Sequence Homology, Amino Acid; Signal Transduction; Tumor Cells, Cultured; src Homology Domains/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GAB1

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GAB1

involved_in

GO:0008286: insulin receptor signaling pathway

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GAB1

enables

GO:0005070: SH3/SH2 adaptor activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete


See also

References

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