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.