Determination of leptin signaling pathways in human and murine keratinocytes.
Recently, we have determined the role of leptin as a keratinocyte mitogen in vitro and during skin repair in vivo. In this study, we assessed leptin-stimulated signal transduction in the human keratinocyte cell line HaCaT and the murine keratinocyte cell line PAM 212. HaCaT keratinocytes were characterized by a constitutive phosphorylation of janus kinase (JAK)-2. By contrast, PAM 212 keratinocytes responded to leptin with a rapid phosphorylation of JAK-2. However, we could determine a cytoplasmic activation of signal transducer and activator of transcription (STAT)-3 by phosphorylation of tyrosine 705 (Y705) within minutes only upon leptin stimulation in both keratinocyte cell lines. Subsequently, STAT-3 translocated to the nucleus where serine 727 (S727) was phosphorylated, establishing a transcriptionally active STAT-3 transcription factor. In a model of cutaneous wound healing, treatment of leptin-deficient obese/obese (ob/ob) mice strongly augmented phosphorylation of STAT-3 (Y705) in wound keratinocytes also in vivo.
Goren
Itamar
I
Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, Germany.
Pfeilschifter
Josef
J
Frank
Stefan
S
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008820:Mice, Obese; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D014945:Wound Healing
D004268:DNA-Binding Proteins; D020738:Leptin; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2