Epidermal growth factor receptor substrate
FunctionEpidermal growth factor receptor substrate 8 (Eps8) is a substrate for receptor tyrosine kinases[1]. Eps8 i overexpressed in human pituitary tumors[2]. Eps8 has a role in amplifying growth factor signaling in human pituitary tumors to promote proliferation and cell survival. Eps8 enable actin binding activity and small GTPase binding activity. The actin bundling activity of Eps8 is hindered by its phosphorylation by kinase. Epidermal growth factor receptor substrate 15 (Eps15) is a component of the endocytic machinery. Eps15 structur is comprised of N-terminal which contains 3 SH3 domains, a central coiled-coil region and a C-terminal region containing multiple copies of Asp-Pro-Phe[3].
DiseaseEps8 promotes cervical cancer metastasis[4]. RelevanceEps8 overexpressing cells are protected from serum withdrawal-induced apoptosis. Structural highlightsThe 3D structure of the complex between Eps8 SH3 domain and the kinase NleH peptide shows [5] (7tzk). The water molecules are shown as red spheres. The C-terminal SAM domain of Eps8 contains the (2e8m) and the phosphorylated Ser residue. Epidermal growth factor receptor substrate 3D structuresEpidermal growth factor receptor substrate 3D structures
|
| ||||||||||
ReferencesReferences
- ↑ Fazioli F, Minichiello L, Matoska V, Castagnino P, Miki T, Wong WT, Di Fiore PP. Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF-dependent mitogenic signals. EMBO J. 1993 Oct;12(10):3799-808. PMID:8404850
- ↑ Xu M, Shorts-Cary L, Knox AJ, Kleinsmidt-DeMasters B, Lillehei K, Wierman ME. Epidermal growth factor receptor pathway substrate 8 is overexpressed in human pituitary tumors: role in proliferation and survival. Endocrinology. 2009 May;150(5):2064-71. PMID:19116338 doi:10.1210/en.2008-1265
- ↑ Salcini AE, Chen H, Iannolo G, De Camilli P, Di Fiore PP. Epidermal growth factor pathway substrate 15, Eps15. Int J Biochem Cell Biol. 1999 Aug;31(8):805-9. PMID:10481267 doi:10.1016/s1357-2725(99)00042-4
- ↑ Li Q, Bao W, Fan Q, Shi WJ, Li ZN, Xu Y, Wu D. Epidermal growth factor receptor kinase substrate 8 promotes the metastasis of cervical cancer via the epithelial-mesenchymal transition. Mol Med Rep. 2016 Oct;14(4):3220-8. PMID:27573546 doi:10.3892/mmr.2016.5638
- ↑ Pollock GL, Grishin AM, Giogha C, Gan J, Oates CV, McMillan PJ, Gaeta I, Tyska MJ, Pearson JS, Scott NE, Cygler M, Hartland EL. Targeting of microvillus protein Eps8 by the NleH effector kinases from enteropathogenic E. coli. Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2204332119. doi:, 10.1073/pnas.2204332119. Epub 2022 Aug 17. PMID:35976880 doi:http://dx.doi.org/10.1073/pnas.2204332119