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A family of mitogen-activated protein kinase-related proteins interacts in vivo with activator protein-1
L R Bernstein1, D K Ferris, N H Colburn
1Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
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.
Insights
This study investigated the in vivo interactions between activator protein-1 (AP-1) and mitogen-activated protein kinases (MAPK). Researchers found that MAP kinase-related proteins associate with AP-1, suggesting a role in gene regulation.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Regulation
Background:
- The activator protein-1 (AP-1) transcription factor is crucial for regulating genes involved in cell growth, differentiation, and cancer.
- Mitogen-activated protein kinases (MAPK) are known to phosphorylate AP-1 components (c-Jun, c-Fos) in vitro, suggesting a role in controlling AP-1 activity.
- However, in vitro interactions do not always reflect in vivo associations, necessitating investigation of direct physical interactions.
Purpose of the Study:
- To determine if MAP kinase-related proteins physically associate with AP-1 components in vivo.
- To identify specific MAP kinase-related proteins that interact with AP-1.
- To elucidate the potential implications of these interactions for gene regulation.
Main Methods:
- Proteins were co-immunoprecipitated using AP-1 antigens.
- Peptide mapping and two-dimensional electrophoretic analyses were employed to detect and characterize interacting proteins.
- In vivo association of MAP kinase-related proteins with AP-1 dimers was analyzed.
Main Results:
- Direct evidence for in vivo association between MAP kinase-related proteins and AP-1 dimers was detected.
- Extracellular signal-regulated kinase-2 (ERK2) was identified as one of the MAP kinase-related proteins binding to AP-1.
- Several novel MAP kinase-related proteins were also found to associate with AP-1.
Conclusions:
- The findings implicate a significant role for MAP kinase-related proteins in AP-1-mediated gene regulation.
- The association of numerous MAP kinase-related proteins with AP-1 suggests a complex regulatory pathway.
- Combinatorial interactions between MAP kinase-related proteins and AP-1 dimers may lead to the formation of distinct complexes, potentially regulating diverse sets of genes.