Coupling of the c-Cbl protooncogene product to ErbB-1/EGF-receptor but not to other ErbB proteins - PubMed (original) (raw)
. 1996 Mar 7;12(5):1117-25.
Affiliations
- PMID: 8649804
Coupling of the c-Cbl protooncogene product to ErbB-1/EGF-receptor but not to other ErbB proteins
G Levkowitz et al. Oncogene. 1996.
Abstract
The ErbB family of transmembrane tyrosine kinases includes the receptor for EGF (ErbB-1), two receptors for NDF/heregulin (ErbB-3 and ErbB-4) and an orphan receptor (ErbB-2). In order to examine the possibility that distinct signal transduction pathways are coupled to each ErbB protein, we examined the interaction of individual ligand-stimulated receptors with the c-Cbl protein, a protooncogene-encoded signaling molecule previously identified in hematopoietic cells. We report that c-Cbl undergoes rapid and sustained phosphorylation on tyrosine residues upon stimulation of fibroblast and epithelial cell lines with ligands of ErbB-1. By contrast, activation of either ErbB-3 or ErbB-4 by NDF did not affect tyrosine phosphorylation of c-Cbl. Likewise, activation of a chimeric ligand-stimulatable ErbB-2 by a heterologous ligand was ineffective. Despite rapidity of the EGF effect, we observed no association of c-Cbl with activated ErbB-1, implying that the interaction is indirect. Our in vitro experiments suggest that a candidate mediator of the interaction is the Grb-2/Ash adaptor protein, which is constitutively bound to c-Cbl. These results indicate that different ErbB proteins can couple to distinct signaling pathways, and therefore their physiological functions are probably non-redundant.
Similar articles
- The C-terminus of the kinase-defective neuregulin receptor ErbB-3 confers mitogenic superiority and dictates endocytic routing.
Waterman H, Alroy I, Strano S, Seger R, Yarden Y. Waterman H, et al. EMBO J. 1999 Jun 15;18(12):3348-58. doi: 10.1093/emboj/18.12.3348. EMBO J. 1999. PMID: 10369675 Free PMC article. - Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.
Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I. Soubeyran P, et al. Nature. 2002 Mar 14;416(6877):183-7. doi: 10.1038/416183a. Nature. 2002. PMID: 11894095 - Negative regulation of ErbB family receptor tyrosine kinases.
Sweeney C, Carraway KL 3rd. Sweeney C, et al. Br J Cancer. 2004 Jan 26;90(2):289-93. doi: 10.1038/sj.bjc.6601500. Br J Cancer. 2004. PMID: 14735165 Free PMC article. Review. - The role of ubiquitylation in signaling by growth factors: implications to cancer.
Shtiegman K, Yarden Y. Shtiegman K, et al. Semin Cancer Biol. 2003 Feb;13(1):29-40. doi: 10.1016/s1044-579x(02)00097-4. Semin Cancer Biol. 2003. PMID: 12507554 Review.
Cited by
- The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer.
O'Neill CE, Sun K, Sundararaman S, Chang JC, Glynn SA. O'Neill CE, et al. Front Physiol. 2024 Mar 27;15:1358850. doi: 10.3389/fphys.2024.1358850. eCollection 2024. Front Physiol. 2024. PMID: 38601214 Free PMC article. Review. - Ubiquitin and its relatives as wizards of the endolysosomal system.
Berlin I, Sapmaz A, Stévenin V, Neefjes J. Berlin I, et al. J Cell Sci. 2023 Feb 15;136(4):jcs260101. doi: 10.1242/jcs.260101. Epub 2023 Feb 24. J Cell Sci. 2023. PMID: 36825571 Free PMC article. - The potential of mRNA expression evaluation in predicting HER2 positivity in gastroesophageal cancer.
Oliveira IM, Nicolau-Neto P, Fernandes PV, Lavigne TS, Neves PF, Tobar JC, Soares-Lima SC, Simão TA, Pinto LFR. Oliveira IM, et al. Braz J Med Biol Res. 2022 Nov 11;55:e12428. doi: 10.1590/1414-431X2022e12428. eCollection 2022. Braz J Med Biol Res. 2022. PMID: 36383805 Free PMC article. - Septins: Regulators of Protein Stability.
Vagin O, Beenhouwer DO. Vagin O, et al. Front Cell Dev Biol. 2016 Dec 20;4:143. doi: 10.3389/fcell.2016.00143. eCollection 2016. Front Cell Dev Biol. 2016. PMID: 28066764 Free PMC article. Review. - Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells.
Marcus EA, Tokhtaeva E, Turdikulova S, Capri J, Whitelegge JP, Scott DR, Sachs G, Berditchevski F, Vagin O. Marcus EA, et al. Biochem J. 2016 Jun 15;473(12):1703-18. doi: 10.1042/BCJ20160203. Epub 2016 Apr 5. Biochem J. 2016. PMID: 27048593 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Research Materials
Miscellaneous