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Convergence of MAP kinase pathways on the ternary complex factor Sap-1a
1Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
The EMBO Journal
|April 1, 1997
Summary
The p38 MAP kinase pathway differentially regulates c-fos transcription via ternary complex factors (TCFs). While Elk-1 is poorly activated, Sap-1a is efficiently phosphorylated by p38, impacting c-fos gene expression.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Regulation
Background:
- The serum response element (SRE) controls c-fos protooncogene transcription.
- Ternary complex factors (TCFs), including Elk-1 and Sap-1a, bind the SRE.
- MAP kinase pathways (ERK, JNK) activate TCFs to trigger c-fos transcription.
Purpose of the Study:
- Investigate the role of p38 MAP kinase in regulating c-fos transcription via TCFs.
- Determine differential activation of Elk-1 and Sap-1a by p38 MAP kinase.
- Elucidate the downstream signaling events linking p38 to c-fos.
Main Methods:
- In vitro and in vivo phosphorylation assays using p38 MAP kinase.
- Site-directed mutagenesis of critical phosphorylation residues on Elk-1 and Sap-1a.
- Reporter gene assays measuring c-fos SRE-dependent transcription.
Main Results:
- p38 MAP kinase poorly phosphorylates Elk-1 at Ser383/Ser389, leading to minimal activation.
- p38 MAP kinase efficiently phosphorylates Sap-1a at Ser381/Ser387, both in vitro and in vivo.
- Mutating Sap-1a phosphorylation sites significantly reduces p38-mediated c-fos transcription.
Conclusions:
- Sap-1a is a key target for p38 MAP kinase signaling in response to mitogens, stress, and apoptosis.
- p38-mediated signaling to Sap-1a and subsequent c-fos transcription exhibits cell-type and promoter specificity.
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