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MAPK plays a pivotal role in reward\u2010related behavior through the activation of certain transcription factors. How D1R signaling regulates behavior through transcription factors remains largely unknown. CREB\u2010binding protein (CBP) promotes transcription through hundreds of different transcription factors and is also important for reward\u2010related behavior. To identify transcription factors regulated by dopamine signaling in MSNs, we performed a phosphoproteomic analysis using affinity beads coated with CBP. We obtained approximately 40 novel candidate proteins in the striatum of the C57BL\/6 mouse brain after cocaine administration. Among them, the megakaryoblastic leukemia\u20102 (MKL2) protein, a transcriptional coactivator of serum response factor (SRF), was our focus. We found that the interaction between CBP and MKL2 was increased by cocaine administration. Additionally, MKL2, CBP and SRF formed a ternary complex in vivo. The C\u2010terminal domain of MKL2 interacted with CBP\u2010KIX and was phosphorylated by MAPK in COS7 cells. The activation of PKA\u2010MAPK signaling induced the nuclear localization of MKL2 and increased SRF\u2010dependent transcriptional activity in neurons. These results demonstrate that dopamine signaling regulates the interaction of MKL2 with CBP in a phosphorylation\u2010dependent manner and thereby controls SRF\u2010dependent gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15303-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:bold>Cover Image for this issue:<\/jats:bold>\u00a0<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15067\">https:\/\/doi.org\/10.1111\/jnc.15067<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15303","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:14:55Z","timestamp":1610756095000},"page":"1774-1788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dynamic subcellular localization and transcription activity of the SRF cofactor MKL2 in the striatum are regulated by MAPK"],"prefix":"10.1111","volume":"157","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7492-0342","authenticated-orcid":false,"given":"Anthony","family":"Ariza","sequence":"first","affiliation":[{"name":"Department of Cell Pharmacology Nagoya University Graduate School of Medicine Nagoya Aichi 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