Antagonistic effects of TGFbeta1 and BMP-6 on skin keratinocyte differentiation.
Several members of the transforming growth factor beta (TGFbeta) superfamily are expressed in the developing murine epidermis. Among these are TGFbeta1, which is found in the basal layer, and bone morphogenetic protein (BMP)-6, located in the suprabasal layers. Although the role of TGFbeta in cell growth has been studied extensively, little is known about the effects of these factors on keratinocyte differentiation. This study demonstrates that BMP-6 acts to positively regulate the differentiation of primary skin keratinocytes grown in culture. In contrast, TGFbeta1 antagonizes keratinocyte differentiation blocking the upregulation of keratin markers by BMP-6. We show that the effects of BMP-6 on expression of keratin 1 (K1), a marker of differentiation, requires signaling through the Smad pathway. In addition, regulation of K1 levels by BMP-6 is modulated by the SEK signaling pathway. This suggests that regulation of keratinocyte differentiation by BMP-6 involves multiple signaling systems.
McDonnell
M A
MA
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee, 37232, USA.
Law
B K
BK
Serra
R
R
Moses
H L
HL
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D015152:Blotting, Northern; D015153:Blotting, Western; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D048670:MAP Kinase Kinase 4; D008297:Male; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D015415:Biomarkers; C525817:Bmp6 protein, mouse; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007633:Keratins; D048670:MAP Kinase Kinase 4; C482562:Map2k4 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases