Related Experiment Video

Updated: Aug 7, 2026

Assay for Adhesion and Agar Invasion in S. cerevisiae
04:36

Assay for Adhesion and Agar Invasion in S. cerevisiae

Published on: November 8, 2006

Convergence of MAP kinase pathways on the ternary complex factor Sap-1a

R Janknecht1, T Hunter

  • 1Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.

The EMBO Journal
|April 1, 1997
PubMed

Insights

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.

More Related Videos

Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System08:54

Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System

Published on: March 20, 2016

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...