AKT and MAPK signaling in KGF-treated and UVB-exposed human epidermal cells.
Regulation of proliferation and differentiation in keratinocyte is a complex and dynamic process that involves activation of multiple signaling pathways triggered by different growth factors. Keratinocyte growth factor (KGF) is not only a potent mitogen, but differently from other growth factors, is a potent inducer of differentiation. The MAP kinase and AKT pathways are involved in proliferation and differentiation of many cell types including keratinocytes. We investigated here the role of KGF in modulating AKT and MAPK activity during differentiation of human keratinocytes. Our results show that the mechanisms of action of KGF are dose-dependent and that a sustained activation of the MAPK signaling cascade causes a negative regulation of AKT. We also demostrated increasing expression of KGFR substrates, such as PAK4 during keratinocyte differentiation parallel to the receptor upregulation.
Lotti
Lavinia Vittoria
LV
Department of Experimental Medicine, University Sapienza, Viale Regina Elena, Rome, Italy.
Rotolo
Sabrina
S
Francescangeli
Federica
F
Frati
Luigi
L
Torrisi
Maria Rosaria
MR
Marchese
Cinzia
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism* / Q000494:pharmacology; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D008565:Membrane Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays; D054462:p21-Activated Kinases
D048868:Adaptor Proteins, Signal Transducing; C106534:FRS2 protein, human; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; C116367:PAK4 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3