title: YAC tripeptide of epidermal growth factor promotes the proliferation of HaCaT keratinocytes through activation of EGFR.
abstract: Epidermal growth factor (EGF) is known to play key roles in skin regeneration and wound-healing. Here, we demonstrate that Pep2-YAC, a tripeptide covering residues 29-31 in the B loop of EGF, promotes the proliferation of HaCaT keratinocytes with activity comparable to EGF. The treatment of HaCaT cells with Pep2-YAC induced phosphorylation, internalization, and degradation of EGFR and organization of signaling complexes, which consist of Grb2, Gab1, SHP2, and PI3K. In addition, it stimulated the phosphorylation of ERK1/2 at Thr 202/Tyr 204 and of Akt1 at Ser 473 and the nuclear translocation of EGFR, STAT3, c-Jun, and c-Fos. These results suggest that Pep2-YAC may be useful as a therapeutic agent for skin regeneration and wound-healing as an EGFR agonist.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Yeon Ho
authors.initials: YH
authors.lastname: Yoo
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Min Seo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Kyeong Han
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Hahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000819:agonists / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; D009842:Oligopeptides; D010455:Peptides; D014157:Transcription Factors; C000598977:tyrosyl-alanyl-cysteine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11