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Updated: Nov 21, 2025

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

Published on: March 20, 2016

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Dynamic subcellular localization and transcription activity of the SRF cofactor MKL2 in the striatum are regulated by

Anthony Ariza1, Yasuhiro Funahashi1,2, Sachi Kozawa1

  • 1Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Journal of Neurochemistry
|January 15, 2021
PubMed

Insights

Dopamine signaling regulates megakaryoblastic leukemia-2 (MKL2) interaction with CREB-binding protein (CBP). This phosphorylation-dependent mechanism controls serum response factor (SRF)-dependent gene expression, impacting reward behavior.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Dopamine type 1 receptor (D1R) signaling in striatal medium spiny neurons (MSNs) activates protein kinase A (PKA) and mitogen-activated protein kinase (MAPK).
  • MAPK is crucial for reward-related behaviors via transcription factor activation.
  • The role of D1R signaling in regulating transcription factors for behavior is not well understood.

Purpose of the Study:

  • To identify transcription factors regulated by dopamine signaling in MSNs.
  • To investigate the role of CREB-binding protein (CBP) in dopamine-mediated transcriptional regulation.
  • To elucidate the mechanism by which dopamine signaling influences reward-related gene expression.

Main Methods:

  • Phosphoproteomic analysis using CBP-affinity beads in mouse striatum after cocaine administration.
  • Co-immunoprecipitation to detect protein-protein interactions.
  • In vitro phosphorylation assays and analysis of transcriptional activity in neurons.

Main Results:

  • Identified approximately 40 novel candidate proteins, including megakaryoblastic leukemia-2 (MKL2), a serum response factor (SRF) coactivator.
  • Cocaine administration increased the interaction between CBP and MKL2.
  • MKL2, CBP, and SRF formed a ternary complex in vivo; MAPK phosphorylated MKL2, promoting its nuclear localization and SRF-dependent transcription.

Conclusions:

  • Dopamine signaling modulates the CBP-MKL2 interaction in a phosphorylation-dependent manner.
  • This mechanism regulates SRF-dependent gene expression in MSNs.
  • The findings provide insights into the molecular basis of reward-related behaviors.

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