PMID- 9923649
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20211203
IS  - 0945-053X (Print)
IS  - 0945-053X (Linking)
VI  - 17
IP  - 8-9
DP  - 1998 Dec
TI  - Enhancement of fibroblast collagenase-1 (MMP-1) gene expression by tumor promoter 
      okadaic acid is mediated by stress-activated protein kinases Jun N-terminal 
      kinase and p38.
PG  - 547-57
AB  - Collagenase-1 (matrix metalloproteinase-1, MMP-1) is expressed by several types 
      of cells, including fibroblasts, and apparently plays an important role in the 
      remodeling of collagenous extracellular matrix in various physiologic and 
      pathologic situations. Here, we have examined the molecular mechanisms of the 
      activation of fibroblast MMP-1 gene expression by a naturally occurring 
      non-phorbol ester type tumor promoter okadaic acid (OA), a potent inhibitor of 
      serine/threonine protein phosphatase 2A. We show that in fibroblasts OA activates 
      three distinct subgroups of mitogen activated protein kinases (MAPKs): 
      extracellular signal-regulated kinase1,2 (ERK1,2), c-Jun 
      N-terminal-kinase/stress-activated protein kinase (JNK/SAPK) and p38. Activation 
      of MMP-1 promoter by OA is entirely blocked by overexpression of dual-specificity 
      MAPK phosphatase CL100. In addition, expression of kinase-deficient forms of 
      ERK1,2, SAPKbeta, p38, or JNK/SAPK kinase SEK1 strongly inhibited OA-elicited 
      activation of MMP-1 promoter. OA-elicited enhancement of MMP-1 mRNA abundance was 
      also strongly prevented by two chemical MAPK inhibitors: PD 98059, a specific 
      inhibitor of the activation of ERK1,2 kinases MEK1,2; and SB 203580, a selective 
      inhibitor of p38 activity. Results of this study show that MMP-1 gene expression 
      in fibroblasts is coordinately regulated by ERK1,2, JNK/SAPK, and p38 MAPKs and 
      suggest an important role for the stress-activated MAPKs JNK/SAPK and p38 in the 
      activation of MMP-1 gene expression. Based on these observations, it is 
      conceivable that specific inhibition of stress-activated MAPK pathways may serve 
      as a novel therapeutic target for inhibiting degradation of collagenous 
      extracellular matrix.
FAU - Westermarck, J
AU  - Westermarck J
AD  - Department of Medical Biochemistry, University of Turku, Finland.
FAU - Holmstrom, T
AU  - Holmstrom T
FAU - Ahonen, M
AU  - Ahonen M
FAU - Eriksson, J E
AU  - Eriksson JE
FAU - Kahari, V M
AU  - Kahari VM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Matrix Biol
JT  - Matrix biology : journal of the International Society for Matrix Biology
JID - 9432592
RN  - 0 (Carcinogens)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - 3T3 Cells
MH  - Adult
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Carcinogens/*metabolism/pharmacology
MH  - Cells, Cultured
MH  - Collagenases/*genetics
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblasts/cytology
MH  - Flavonoids/pharmacology
MH  - *Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases
MH  - MAP Kinase Kinase 1
MH  - MAP Kinase Kinase 2
MH  - Male
MH  - Matrix Metalloproteinase 1
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - *Mitogen-Activated Protein Kinases
MH  - Okadaic Acid/*metabolism/pharmacology
MH  - Promoter Regions, Genetic
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Pyridines/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/01/29 00:00
MHDA- 1999/01/29 00:01
CRDT- 1999/01/29 00:00
PHST- 1999/01/29 00:00 [pubmed]
PHST- 1999/01/29 00:01 [medline]
PHST- 1999/01/29 00:00 [entrez]
AID - S0945-053X(98)90107-X [pii]
AID - 10.1016/s0945-053x(98)90107-x [doi]
PST - ppublish
SO  - Matrix Biol. 1998 Dec;17(8-9):547-57. doi: 10.1016/s0945-053x(98)90107-x.