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PMID:7513704

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Citation

Sasaoka, T, Rose, DW, Jhun, BH, Saltiel, AR, Draznin, B and Olefsky, JM (1994) Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-1, and epidermal growth factor. J. Biol. Chem. 269:13689-94

Abstract

Shc proteins contain a single SH2 domain, lack catalytic activity, and are substrates for activated receptors for insulin, insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF). Treatment with these growth factors induced rapid tyrosine phosphorylation of Shc. We investigated the potential role of Shc in mitogenic signaling. Affinity-purified antibodies were microinjected into living Rat1 fibroblasts overexpressing human insulin receptors. Bromodeoxyuridine incorporation into newly synthesized DNA was subsequently studied to assess the importance of Shc. Cellular microinjection of anti-Shc antibody inhibited BrdU incorporation induced by insulin, IGF-1, and EGF, but did not affect cells stimulated by fetal calf serum. Microinjection of an oncogenic p21ras protein (T24) into quiescent cells produced constitutively active mitogenic signaling, and comicroinjection of T24 with the anti-Shc antibody restored insulin and EGF stimulation of DNA synthesis. Immunoprecipitates of Shc from lysates of insulin-stimulated cells removed 70-80% of guanine nucleotide-releasing factor activity. These results indicate that Shc is an important component in a mitogenic signal transduction pathway that is shared by insulin, IGF-1, and EGF. The functional locus of Shc is either upstream of p21ras or lies on a distinct branch of the pathway leading to cell cycle progression.

Links

PubMed

Keywords

Animals; Cell Line; Epidermal Growth Factor/pharmacology; Humans; Insulin/pharmacology; Insulin-Like Growth Factor I/pharmacology; Mitogens/pharmacology; Phosphorylation; Proteins/chemistry; Proteins/physiology; Proto-Oncogene Proteins pp60(c-src); Rats; Receptor, Insulin/genetics; Signal Transduction; Transfection

Significance

Annotations

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

PIG:IGF1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:Q9QX70

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q5M824

F

Seeded From UniProt

complete

RAT:Q9QX70

part_of

GO:0070435: Shc-EGFR complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:SHC1

involved_in

GO:0008284: positive regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SHC1

part_of

GO:0070435: Shc-EGFR complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:SHC1

involved_in

GO:0008286: insulin receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:SHC1

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9QX70

F

Seeded From UniProt

complete

PIG:INS

involved_in

GO:0045740: positive regulation of DNA replication

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

PIG:INS

involved_in

GO:0046628: positive regulation of insulin receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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