Abstract
Cells organize diverse types of specialized adhesion sites upon attachment to extracellular matrix (ECM) components. One of the physiological roles of such cell-ECM interactions is to initiate and regulate adhesion-mediated signal transduction responses. The association of cells with fibronectin fibrils has been shown to regulate the JNK and p38 signaling pathways. We tested whether tensin, a cytoskeletal component localized to both focal contacts and fibronectin-associated fibrillar adhesions, can induce these signaling pathways. We found that tensin overexpression resulted in activation of both the c-Jun amino-terminal kinase (JNK) and p38 pathways. Tensin-mediated JNK activation was independent of the activities of the small GTP binding proteins Rac and Cdc42, but did depend on SEK, a kinase involved in the JNK pathway. We suggest that tensin may directly activate the JNK and p38 pathways, acting downstream or independent of the activities of the small GTP binding proteins Rac and Cdc42.
Copyright 2000 Academic Press.
MeSH terms
-
Calcium-Calmodulin-Dependent Protein Kinases / genetics
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
-
Cell Line
-
Enzyme Activation
-
Focal Adhesion Kinase 1
-
Focal Adhesion Protein-Tyrosine Kinases
-
Genes, Dominant / genetics
-
Humans
-
JNK Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase 4*
-
MAP Kinase Kinase 6
-
MAP Kinase Signaling System*
-
Microfilament Proteins / genetics
-
Microfilament Proteins / metabolism*
-
Mitogen-Activated Protein Kinase Kinases / genetics
-
Mitogen-Activated Protein Kinase Kinases / metabolism
-
Mitogen-Activated Protein Kinases / genetics
-
Mitogen-Activated Protein Kinases / metabolism*
-
Models, Biological
-
Mutation / genetics
-
Protein-Tyrosine Kinases / genetics
-
Protein-Tyrosine Kinases / metabolism
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Tensins
-
Transfection
-
cdc42 GTP-Binding Protein / genetics
-
cdc42 GTP-Binding Protein / metabolism
-
p38 Mitogen-Activated Protein Kinases
-
rac GTP-Binding Proteins / genetics
-
rac GTP-Binding Proteins / metabolism
Substances
-
Microfilament Proteins
-
Recombinant Fusion Proteins
-
Tensins
-
Protein-Tyrosine Kinases
-
Focal Adhesion Kinase 1
-
Focal Adhesion Protein-Tyrosine Kinases
-
PTK2 protein, human
-
Calcium-Calmodulin-Dependent Protein Kinases
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase 4
-
MAP Kinase Kinase 6
-
MAP2K4 protein, human
-
MAP2K6 protein, human
-
Mitogen-Activated Protein Kinase Kinases
-
cdc42 GTP-Binding Protein
-
rac GTP-Binding Proteins