2015年4月
PCTK1 Regulates Integrin-Dependent Spindle Orientation via Protein Kinase A Regulatory Subunit KAP0 and Myosin X
MOLECULAR AND CELLULAR BIOLOGY
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- 巻
- 35
- 号
- 7
- 開始ページ
- 1197
- 終了ページ
- 1208
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1128/MCB.01017-14
- 出版者・発行元
- AMER SOC MICROBIOLOGY
Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation. However, the signaling pathways that couple integrins to spindle orientation remain elusive. Here, we show that PCTAIRE-1 kinase (PCTK1), a member of the cyclin-dependent kinases (CDKs) whose function is poorly characterized, plays an essential role in this process. PCTK1 regulates spindle orientation in a kinase-dependent manner. Phosphoproteomic analysis together with an RNA interference screen revealed that PCTK1 regulates spindle orientation through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase A (PKA). This phosphorylation is dispensable for KAP0 dimerization and for PKA binding but is necessary for its interaction with myosin X, a regulator of spindle orientation. KAP0 binds to the FERM domain of myosin X and enhances the association of myosin X-FERM with beta 1 integrin. This interaction between myosin X-FERM and beta 1 integrin appeared to be crucial for spindle orientation control. We propose that PCTK1-KAP0-myosin X-beta 1 integrin is a functional module providing a link between ECM and the actin cytoskeleton in the ECM-dependent control of spindle orientation.
- リンク情報
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- DOI
- https://doi.org/10.1128/MCB.01017-14
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/25605337
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355539
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000351739200010&DestApp=WOS_CPL
- URL
- http://europepmc.org/articles/PMC4355539
- URL
- http://orcid.org/0000-0001-7633-8495
- ID情報
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- DOI : 10.1128/MCB.01017-14
- ISSN : 0270-7306
- eISSN : 1098-5549
- ORCIDのPut Code : 58378583
- PubMed ID : 25605337
- PubMed Central 記事ID : PMC4355539
- Web of Science ID : WOS:000351739200010