A family of mitogen-activated protein kinase-related proteins interacts in vivo with activator protein-1 transcription factor.
The activator protein-1 (AP-1) transcription factor modulates expression of genes involved in growth regulation, differentiation, and neoplastic transformation. Several mitogen-activated protein kinases (MAP kinases) as well as other kinases phosphorylate c-Jun and c-Fos in vitro and are postulated to control AP-1 activity. However, since many protein kinases phosphorylate substrates in vitro with which they have no association in vivo, we sought evidence for interaction in vivo between AP-1 and MAP kinase proteins. We now report detection of an association in vivo of MAP kinase-related proteins with c-Jun and AP-1 dimers by peptide mapping and two-dimensional electrophoretic analyses of proteins co-immunoprecipitated with AP-1 antigens. Extracellular signal-regulated kinase-2 and several apparently novel MAP kinase-related proteins are among the species that bind to AP-1. The large number of MAP kinase-related proteins associated with AP-1 implicates them on an important gene regulation pathway. Combinatorial association between MAP kinase-related proteins and AP-1 dimers could potentially create numerous distinct complexes that could regulate diverse genes.
Bernstein
L R
LR
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Ferris
D K
DK
Colburn
N H
NH
Sobel
M E
ME
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004817:Epidermis; D046911:Macromolecular Substances; D019950:Mitogen-Activated Protein Kinase 1; D048053:Mitogen-Activated Protein Kinase 6; D020928:Mitogen-Activated Protein Kinases; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000032:analysis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000302:isolation & purification / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012697:Serine Endopeptidases
D046911:Macromolecular Substances; D010748:Phosphopeptides; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048053:Mitogen-Activated Protein Kinase 6; D020928:Mitogen-Activated Protein Kinases; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase