PCTK1 Regulates Integrin-Dependent Spindle Orientation via Protein Kinase A Regulatory Subunit KAP0 and Myosin X |
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| Authors: | Sayaka Iwano Ayaka Satou Shigeru Matsumura Naoyuki Sugiyama Yasushi Ishihama Fumiko Toyoshima |
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| Institution: | aDepartment of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan;bDepartment of Cell Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Japan;cDepartment of Molecular & Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan |
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| Abstract: | 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 β1 integrin. This interaction between myosin X-FERM and β1 integrin appeared to be crucial for spindle orientation control. We propose that PCTK1-KAP0-myosin X-β1 integrin is a functional module providing a link between ECM and the actin cytoskeleton in the ECM-dependent control of spindle orientation. |
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