scholarly journals The Mitogen-activated Protein Kinase and JAK-STAT Signaling Pathways Are Required for an Oncostatin M-responsive Element-mediated Activation of Matrix Metalloproteinase 1 Gene Expression

1997 ◽  
Vol 272 (2) ◽  
pp. 1188-1196 ◽  
Author(s):  
Edward Korzus ◽  
Hideaki Nagase ◽  
Russell Rydell ◽  
James Travis
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Matrix Metalloproteinase ◽  
Signaling Pathways ◽  
Oncostatin M ◽  
Mitogen Activated Protein Kinase ◽  
Matrix Metalloproteinase 1 ◽  
Stat Signaling ◽  
Mitogen Activated Protein ◽  
Responsive Element

scholarly journals Selective loss of PMA-stimulated expression of matrix metalloproteinase 1 in HaCaT keratinocytes is correlated with the inability to induce mitogen-activated protein family kinases

1999 ◽  
Vol 339 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Barry D. SUDBECK ◽  
Petra BAUMANN ◽  
Gavin J. RYAN ◽  
Katja BREITKOPF ◽  
Roswitha NISCHT ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Matrix Metalloproteinase ◽  
Map Kinase ◽  
Map Kinases ◽  
Specific Inhibitor ◽  
Hacat Cells ◽  
Hacat Keratinocytes ◽  
Matrix Metalloproteinase 1 ◽  
Mitogen Activated Protein

Many cell types, including fibroblasts and primary keratinocytes, increase matrix metalloproteinase 1 (MMP-1) production in response to agonists such as growth factors and phorbol esters. However, the spontaneously transformed human keratinocyte cell line HaCaT, although it increases MMP-1 production in response to epidermal growth factor (EGF), does not respond similarly to stimulation with PMA. This phenomenon occurs even though HaCaT cells remain proliferatively responsive to both agonists, suggesting a HaCaT-specific defect in a PMA-mediated signal transduction pathway. Using an inside-out approach to elucidate the source of this defect, we found that EGF, but not PMA, stimulated MMP-1 promoter activity in transiently transfected HaCaT keratinocytes. In addition, an assessment of fibroblast and HaCaT c-fos and c-jun gene expression after exposure to EGF and PMA showed that although both agonists increased the expression of c-fos and c-jun mRNA in fibroblasts, only EGF did so in HaCaT keratinocytes. Finally, we looked at the activation of mitogen-activated protein (MAP) family kinases after stimulation with EGF or PMA and found that both agonists increased the phosphorylation and activation of fibroblast extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but only EGF activated the same kinase activities in HaCaT cells. Further, the EGF-mediated increase in MMP-1 gene expression was inhibited by the MAP kinase/ERK kinase (MEK)-specific inhibitor PD98059 and the p38 kinase-specific inhibitor SB203580. Our evidence indicates that although HaCaT MAP kinases are functional, they are not properly regulated in response to the activation of protein kinase C, and that the defect that bars HaCaT MMP-1 expression in response to stimulation with PMA lies before MAP kinase activation.

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