Insulin and EGF receptors integrate the Ras and Rap signaling pathways

Jeffrey E. Pessin, Shuichi Okada

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Ras is a low molecular weight (Mr 21,000) GTP binding protein that plays an essential role in cell proliferation and differentiation. Mutations that result in constitutive activation of Ras are associated with several types of neoplastic tissue in mammals and expression of these alleles into cultured fibroblasts results in cellular transformation. Opposing the Ras activation pathway, the low molecular GTP binding protein Rap was originally observed to revert or suppress the transformed phenotype in K1-Ras-transformed fibroblasts. This apparent antagonism between Ras and Rap function may reflect the ability of Rap and Ras to interact with the same downstream effectors, since these proteins share identical sequences within their respective effector domains. Although the precise molecular details remained to be established, there is a substantial similarity in the upstream signaling mechanisms that regulate both Ras and Rap activation. Ras GTP binding is stimulated upon the targeting of the Ras guanylnucleotide exchange factor SOS to the plasma membrane location of Ras. The carboxyl terminal domain of SOS contains a proline-rich regions that directs its association with the SH3 domains of the small adapter protein, Grb2. Similarly, the formation of active GTP-bound Rap results from the specific interaction with the Rap guanylnucleotide exchange factor C3G which specifically associates with the central SH3 domain of the small adapter protein, CrkII. Thus, efficient regulation of receptor tyrosine kinase downstream signaling events require the coordinate interplay of these two pathways.

Original languageEnglish (US)
JournalEndocrine Journal
Volume46
Issue numberSUPPL.
StatePublished - Mar 1999
Externally publishedYes

Fingerprint

src Homology Domains
rap GTP-Binding Proteins
Guanosine Triphosphate
Proto-Oncogene Proteins c-crk
Fibroblasts
Insulin
Receptor Protein-Tyrosine Kinases
GTP-Binding Proteins
Proline
Cell Differentiation
Mammals
Proteins
Molecular Weight
Alleles
Cell Proliferation
Cell Membrane
Phenotype
Mutation
ErbB Receptors

Keywords

  • Epidermal growth factor
  • Insulin
  • Rap
  • Ras
  • Tyrosine kinase

ASJC Scopus subject areas

  • Endocrinology

Cite this

Insulin and EGF receptors integrate the Ras and Rap signaling pathways. / Pessin, Jeffrey E.; Okada, Shuichi.

In: Endocrine Journal, Vol. 46, No. SUPPL., 03.1999.

Research output: Contribution to journalArticle

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