Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells.
SEK-1, a dual specificity protein kinase that serves as one of the immediate upstream activators of the stress-activated protein kinases (SAPKs), associates specifically with the actin-binding protein, ABP-280, in vitro and in situ. SEK-1 binds to the carboxyl-terminal rod segment of ABP-280, upstream of the ABP carboxyl-terminal dimerization domain. Activation ... of SEK-1 in situ increases the SEK-1 activity bound to ABP-280 without changing the amount of SEK-1 polypeptide bound. The influence of ABP-280 on SAPK regulation was evaluated in human melanoma cells that lack ABP-280 expression, and in stable transformants of these cells expressing wild type ABP, or an actin-binding but dimerization-deficient mutant ABP (ABPDeltaCT109). ABP-280-deficient cells show an activation of SAPK in response to most stimuli that is comparable to that seen in ABP-280-replete cells; ABP-280-deficient cells, however, fail to show the brisk tumor necrosis factor-alpha (TNF-alpha) activation of SAPK seen in ABP-replete cells and have an 80% reduction in SAPK activation by lysophosphatidic acid. Expression of the dimerization-deficient mutant ABP-280 fails to correct the defective SAPK response to lysophosphatidic acid, but essentially normalizes the TNF-alpha activation of SAPK. Thus, a lack of ABP-280 in melanoma cells causes a defect in the regulation of SAPK that is selective for TNF-alpha and is attributable to the lack of ABP-280 polypeptide itself rather than to the disordered actin cytoskeleton that results therefrom. ABP-280 participates in TNF-alpha signal transduction to SAPKs, in part through the binding of SEK-1.
Mesh Terms:
Actins, Animals, Anisomycin, B-Lymphocytes, Cell Line, Contractile Proteins, Dimerization, Enzyme Activation, Epidermal Growth Factor, Glutathione Transferase, Humans, MAP Kinase Kinase 4, Melanoma, Mice, Microfilament Proteins, Mitogen-Activated Protein Kinase Kinases, Mutagenesis, Site-Directed, Phosphorylation, Protein Kinases, Recombinant Fusion Proteins, T-Lymphocytes, Transfection, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha
Actins, Animals, Anisomycin, B-Lymphocytes, Cell Line, Contractile Proteins, Dimerization, Enzyme Activation, Epidermal Growth Factor, Glutathione Transferase, Humans, MAP Kinase Kinase 4, Melanoma, Mice, Microfilament Proteins, Mitogen-Activated Protein Kinase Kinases, Mutagenesis, Site-Directed, Phosphorylation, Protein Kinases, Recombinant Fusion Proteins, T-Lymphocytes, Transfection, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha
J. Biol. Chem.
Date: Jan. 31, 1997
PubMed ID: 9006895
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