p62 functions as a p38 MAP kinase regulator.
By screening a HeLa cDNA library to isolate genes encoding p38-regulating proteins, we have isolated two independent clones which encode the binding proteins to p38. We have found that both of these cDNA clones encode p62, first identified as a phosphorylation independent p56(lck) SH2 domain binding protein. Recent studies also indicate that p62 interacts with atypical PKCs to anchor them to intracellular membranes and with RIP to mediate signals to NF-kappaB through atypical PKCs. Moreover, p62 is shown to be involved in the transcriptional regulation via SV40 enhancer and to serve as a coactivator of an orphan nuclear hormone receptor. A coimmunoprecipitation assay shows its enhanced association in HeLa cells after stimulations such as sorbitol and anisomycin. An indirect immunofluorescence study indicates that p62 colocalizes with p38 in the nucleus in response to the stimulation. And in vitro kinase assays using MBP, but not ATF-2, as a substrate show that p62 enhances p38 activities in a dose-dependent manner. Together, these results demonstrate that p62 plays roles not only as an anchor but also as a regulator for the p38 kinase activity.
Sudo
T
T
Antibiotics Laboratory, Biodesign Group, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Maruyama
M
M
Osada
H
H
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017931:DNA Primers; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation; D000071456:Sequestosome-1 Protein; D013347:Subcellular Fractions / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D004676:Myelin Basic Protein; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases