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.
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Sequence
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Cell Line
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Proliferation / drug effects
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Epidermal Growth Factor / pharmacology*
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ErbB Receptors / agonists
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ErbB Receptors / metabolism*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Keratinocytes / cytology*
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Keratinocytes / drug effects
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Keratinocytes / metabolism*
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Molecular Sequence Data
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Peptides / chemistry
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Peptides / pharmacology*
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Protein Transport / drug effects
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Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction / drug effects
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Transcription Factors / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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GAB1 protein, human
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Oligopeptides
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Peptides
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Transcription Factors
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tyrosyl-alanyl-cysteine
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Epidermal Growth Factor
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ErbB Receptors
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Protein Tyrosine Phosphatase, Non-Receptor Type 11