YAC tripeptide of epidermal growth factor promotes the proliferation of HaCaT keratinocytes through activation of EGFR
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Epidermal growth factor (EGF) is known to play key roles inskin regeneration and wound-healing. Here, we demonstratethat Pep2-YAC, a tripeptide covering residues 29-31 in the Bloop of EGF, promotes the proliferation of HaCaT keratinocyteswith activity comparable to EGF. The treatment of HaCaT cellswith Pep2-YAC induced phosphorylation, internalization, anddegradation of EGFR and organization of signaling complexes,which consist of Grb2, Gab1, SHP2, and PI3K. In addition, itstimulated the phosphorylation of ERK1/2 at Thr 202/Tyr 204and of Akt1 at Ser 473 and the nuclear translocation of EGFR,STAT3, c-Jun, and c-Fos. These results suggest that Pep2-YACmay be useful as a therapeutic agent for skin regeneration andwound-healing as an EGFR agonist.
Abstract
Epidermal growth factor (EGF) is known to play key roles inskin regeneration and wound-healing. Here, we demonstratethat Pep2-YAC, a tripeptide covering residues 29-31 in the Bloop of EGF, promotes the proliferation of HaCaT keratinocyteswith activity comparable to EGF. The treatment of HaCaT cellswith Pep2-YAC induced phosphorylation, internalization, anddegradation of EGFR and organization of signaling complexes,which consist of Grb2, Gab1, SHP2, and PI3K. In addition, itstimulated the phosphorylation of ERK1/2 at Thr 202/Tyr 204and of Akt1 at Ser 473 and the nuclear translocation of EGFR,STAT3, c-Jun, and c-Fos. These results suggest that Pep2-YACmay be useful as a therapeutic agent for skin regeneration andwound-healing as an EGFR agonist.
참고문헌 (26)
- Doma, E., "EGFR-ras-raf signaling in epidermal stem cells: roles in hair follicle development, regeneration, tissue remodeling and epidermal cancers", Int. J. Mol. Sci, 14, pp.19361~19384 (2013)
- Nanba, D., "Recent advances in the epidermal growth factor receptor", ligand system biology on skin homeostasis and keratinocyte stem cell regulation, 2013, pp.72, 81~86
- Yarden, Y., "Untangling the ErbB signalling network", Nat. Rev. Mol. Cell Biol, 2, pp.127~137 (2001)
- Hynes, N. E., "ERBB receptors and cancer: the complexity of targeted inhibitors", Nat. Rev. Cancer, 5, pp.341~354 (2005)
- Ching, Y. H., "The use of growth factors and other humoral agents to accelerate and enhance burn wound healing", Eplasty, 11, pp.e41~ (2011)
- Gembitsky, D. S., "A specific binding site for a fragment of the B-loop of epidermal growth factor and related peptides", Peptides, 23, pp.97~102 (2002)
- Dreux, A. C., "The epidermal growth factor receptors and their family of ligands: Their putative role in atherogenesis", Atherosclerosis, 186, pp.38~53 (2006)
- Ogiso, H., "Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains", Cell, 110, pp.775~787 (2002)
- Komoriya, A., "Biologically active synthetic fragments of epidermal growth factor: localization of a major receptor-binding region", Proc. Natl. Acad. Sci. U.S.A, 81, pp.1351~1355 (1984)
- Pastore, S., "The epidermal growth factor receptor system in skin repair and inflammation", J. Invest. Dermatol, 128, pp.1365~1374 (2008)
- Prausnitz, M. R., "Transdermal drug delivery", Nat. Biotechnol, 26, pp.1261~1268 (2008)
- Guo, A, "Signaling networks assembled by oncogenic EGFR and c-Met", Proc. Natl. Acad. Sci. U.S.A, 105, pp.692~697 (2008)
- Bancroft, C. C., "Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF-κB and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines", Int. J. Cancer, 99, pp.538~548 (2002)
- Chan, K. S., "Epidermal growth factor receptor- mediated activation of Stat3 during multistage skin carcinogenesis", Cancer Res, 64, pp.2382~2389 (2004)
- Nakamura, T., "Peptide mimics of epidermal growth factor (EGF) with antagonistic activity", J. Biotechnol, 116, pp.211~219 (2005)
- Nemoto, W., "Recent advances in functional region prediction by using structural and evolutionary information - Remaining problems and future extensions", Comput. Struct. Biotechnol. J, 8, pp.e201308007~ (2013)
- Lo, H. W., "EGFR signaling pathway in breast cancers: from traditional signal transduction to direct nuclear translocalization", Breast. Cancer Res. Treat, 95, pp.211~218 (2006)
- Gu, H., "The "Gab" in signal transduction", Trends. Cell Biol, 13, pp.122~130 (2003)
- Yart, A., "A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen- activated protein kinases by epidermal growth factor", J. Biol. Chem, 276, pp.8856~8864 (2001)
- Rodrigues, G. A., "A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling", Mol. Cell. Biol, 20, pp.1448~1459 (2000)
- Liebmann, C., "Regulation of MAP kinase activity by peptide receptor signalling pathway: paradigms of multiplicity", Cell. Signal, 13, pp.777~785 (2001)
- Vivanco, I., "The phosphatidylinositol 3-Kinase AKT pathway in human cancer", Nat. Rev. Cancer, 2, pp.489~501 (2002)
- Kirisits, A., "Epidermal growth factor receptor degradation: an alternative view of oncogenic pathways", Int. J. Biochem. Cell Biol, 39, pp.2173~2182 (2007)
- Lo, H. -W., "Nuclear interaction of EGFR and STAT3 in the activation of the iNOS", NO pathway, 2005, pp.7, 575~589
- Debidda, M., "A role of STAT3 in Rho GTPase-regulated cell migration and proliferation", J. Biol. Chem, 280, pp.17275~17285 (2005)
- Bild, A. H., "Cytoplasmic transport of Stat3 by receptor-mediated endocytosis", EMBO J, 21, pp.3255~3263 (2002)
