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PMID:8305738

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Citation

Stern, MJ, Marengere, LE, Daly, RJ, Lowenstein, EJ, Kokel, M, Batzer, A, Olivier, P, Pawson, T and Schlessinger, J (1993) The human GRB2 and Drosophila Drk genes can functionally replace the Caenorhabditis elegans cell signaling gene sem-5. Mol. Biol. Cell 4:1175-88

Abstract

Mutations in the Caenorhabditis elegans gene sem-5 affect cell signaling processes involved in guiding a class of cell migrations and inducing vulval cell fates. The sem-5 sequence encodes a protein comprised almost exclusively of SH2 and SH3 domains (SH, src homology region) that are found together in many signaling proteins and nonreceptor tyrosine kinases. A human protein, GRB2, was identified by its ability to associate with the activated human epidermal growth factor receptor (hEGFR). The GRB2 and Sem-5 proteins share an identical architecture of their SH2 and SH3 domains and 58% amino acid sequence identity. Here we demonstrate that GRB2 and a Drosophila sem-5-like gene Drk can specifically rescue sem-5 mutants. We also show that Sem-5, like GRB2, can bind to the activated hEGFR in vitro. We further correlate the abilities of several mutant variants of GRB2 and Sem-5 to bind to the hEGFR in vitro with their abilities to functionally replace sem-5 in vivo. These data indicate that GRB2 and Drk are functional homologues of Sem-5 and demonstrate the high degree of conservation of both structure and function between signaling systems throughout evolution.

Links

PubMed PMC275752

Keywords

Adaptor Proteins, Signal Transducing; Animals; Animals, Genetically Modified; Base Sequence; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins; Cloning, Molecular; Drosophila Proteins; Female; GRB2 Adaptor Protein; Genes, Helminth; Genes, Insect/genetics; Helminth Proteins/genetics; Humans; Insect Hormones/genetics; Molecular Sequence Data; Mutagenesis, Site-Directed; Point Mutation/genetics; Proteins/genetics; Receptor, Epidermal Growth Factor/analysis; Receptor, Epidermal Growth Factor/genetics; Receptor, Epidermal Growth Factor/metabolism; Receptors, Platelet-Derived Growth Factor/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/isolation & purification; Signal Transduction/genetics; Transformation, Genetic; Vulva/growth & development

Significance

Annotations

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

HUMAN:EGFR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P29355

F

Seeded From UniProt

complete

CAEEL:SEM5

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P00533

F

Seeded From UniProt

complete

Notes

See also

References

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