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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.
Biochem J. 1999 Apr 01; 339 (Pt 1):167-75.BJ

Abstract

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.

Authors+Show Affiliations

Department of Dermatology, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10085241

Citation

Sudbeck, B D., et al. "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." The Biochemical Journal, vol. 339 (Pt 1), 1999, pp. 167-75.
Sudbeck BD, Baumann P, Ryan GJ, et al. 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. Biochem J. 1999;339 (Pt 1):167-75.
Sudbeck, B. D., Baumann, P., Ryan, G. J., Breitkopf, K., Nischt, R., Krieg, T., & Mauch, C. (1999). 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. The Biochemical Journal, 339 (Pt 1), 167-75.
Sudbeck BD, et al. 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. Biochem J. 1999 Apr 1;339 (Pt 1):167-75. PubMed PMID: 10085241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Sudbeck,B D, AU - Baumann,P, AU - Ryan,G J, AU - Breitkopf,K, AU - Nischt,R, AU - Krieg,T, AU - Mauch,C, PY - 1999/3/23/pubmed PY - 1999/3/23/medline PY - 1999/3/23/entrez SP - 167 EP - 75 JF - The Biochemical journal JO - Biochem. J. VL - 339 (Pt 1) N2 - 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. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/10085241/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_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/10085241/ DB - PRIME DP - Unbound Medicine ER -