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 expressi on of genes involved in growth regulation, differentiation, and neopla stic transformation. Several mitogen-activated protein kinases (MAP ki nases) as well as other kinases phosphorylate c-Jun and c-Fos in vitro and are postulated to control AP-1 activity. However, since many prot ein kinases phosphorylate substrates in vitro with which they have no association in vivo, we sought evidence for interaction in vivo betwee n AP-1 and MAP kinase proteins. We now report detection of an associat ion in vivo of MAP kinase-related proteins with c-Jun and AP-1 dimers by peptide mapping and two-dimensional electrophoretic analyses of pro teins co-immunoprecipitated with AP-1 antigens. Extracellular signal-r egulated kinase-2 and several apparently novel MAP kinase-related prot eins 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 imp ortant gene regulation pathway. Combinatorial association between MAP kinase-related proteins and AP-1 dimers could potentially create numer ous distinct complexes that could regulate diverse genes.