Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor
- PMID: 8490966
- DOI: 10.1016/0092-8674(93)90146-h
Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor
Abstract
Antisera against murine Son of sevenless (Sos) recognize a protein of M(r) 155,000 in rat-1 fibroblasts with specific guanine nucleotide exchange activity toward p21c-Ha-ras. Epidermal growth factor (EGF) receptor coimmunoprecipitates with Sos from EGF-stimulated, but not quiescent, cells. The SH2 and SH3 domain-containing "adapter" protein Grb2 is also found in Sos immunoprecipitates in an EGF-inducible manner. In vitro reconstitution shows that Grb2 is required for the binding of activated EGF receptor to Sos. A phosphopeptide corresponding to tyrosine 1068 of the EGF receptor blocks both the assembly of the complex and EGF stimulation of nucleotide exchange on p21ras in a permeabilized cell system. These results suggest that EGF-induced activation of nucleotide exchange on p21ras proceeds through the recruitment of cytosolic Sos to a complex with EGF receptor and Grb2 at the plasma membrane.
Similar articles
-
Involvement of Shc in insulin- and epidermal growth factor-induced activation of p21ras.Mol Cell Biol. 1994 Mar;14(3):1575-81. doi: 10.1128/mcb.14.3.1575-1581.1994. Mol Cell Biol. 1994. PMID: 8114695 Free PMC article.
-
Divergent mechanisms for homologous desensitization of p21ras by insulin and growth factors.J Biol Chem. 1995 Oct 6;270(40):23421-8. doi: 10.1074/jbc.270.40.23421. J Biol Chem. 1995. PMID: 7559502
-
SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases.J Biol Chem. 1994 May 13;269(19):14081-7. J Biol Chem. 1994. PMID: 8188688
-
The GRB2/Sem-5 adaptor protein.FEBS Lett. 1994 Jan 31;338(2):113-7. doi: 10.1016/0014-5793(94)80346-3. FEBS Lett. 1994. PMID: 8307166 Review.
-
Inhibitors of Ras signal transduction as antitumor agents.Biochem Pharmacol. 2000 Oct 15;60(8):1165-9. doi: 10.1016/s0006-2952(00)00428-7. Biochem Pharmacol. 2000. PMID: 11007954 Review.
Cited by
-
Oncogenic mutations of KRAS modulate its turnover by the CUL3/LZTR1 E3 ligase complex.Life Sci Alliance. 2024 Mar 7;7(5):e202302245. doi: 10.26508/lsa.202302245. Print 2024 May. Life Sci Alliance. 2024. PMID: 38453365 Free PMC article.
-
Role of Actin-Binding Proteins in Skeletal Myogenesis.Cells. 2023 Oct 25;12(21):2523. doi: 10.3390/cells12212523. Cells. 2023. PMID: 37947600 Free PMC article. Review.
-
Mutant HRas Signaling and Rationale for Use of Farnesyltransferase Inhibitors in Head and Neck Squamous Cell Carcinoma.Target Oncol. 2023 Sep;18(5):643-655. doi: 10.1007/s11523-023-00993-3. Epub 2023 Sep 4. Target Oncol. 2023. PMID: 37665491 Review.
-
Protein quality control machinery supports primary ciliogenesis by eliminating GDP-bound Rab8-family GTPases.iScience. 2023 Apr 10;26(5):106652. doi: 10.1016/j.isci.2023.106652. eCollection 2023 May 19. iScience. 2023. PMID: 37182096 Free PMC article.
-
In vivo CRISPR screens identify RhoV as a pro-metastasis factor of triple-negative breast cancer.Cancer Sci. 2023 Jun;114(6):2375-2385. doi: 10.1111/cas.15783. Epub 2023 Mar 27. Cancer Sci. 2023. PMID: 36898847 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
