title: Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l γ.
abstract: Focal adhesions (FAs) are highly dynamic structures that are assembled and disassembled on a continuous basis. The balance between the two processes mediates various aspects of cell behavior, ranging from cell adhesion and spreading to directed cell migration. The turnover of FAs is regulated at multiple levels and involves a variety of signaling molecules and adaptor proteins. In the present study, we show that in response to integrin engagement, a subcellular pool of Protein Kinase D1 (PKD1) localizes to the FAs. PKD1 affects FAs by decreasing turnover and promoting maturation, resulting in enhanced cell adhesion. The effects of PKD1 are mediated through direct phosphorylation of FA-localized phosphatidylinositol-4-phosphate 5-kinase type-l γ (PIP5Klγ) at serine residue 448. This phosphorylation occurs in response to Fibronectin-RhoA signaling and leads to a decrease in PIP5Klγs' lipid kinase activity and binding affinity for Talin. Our data reveal a novel function for PKD1 as a regulator of FA dynamics and by identifying PIP5Klγ as a novel PKD1 substrate provide mechanistic insight into this process.
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors: Nisha
authors: N
authors: Durand
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors: Ligia I
authors: LI
authors: Bastea
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors: Jason
authors: J
authors: Long
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors: Heike
authors: H
authors: Döppler
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors: Kun
authors: K
authors: Ling
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors: Peter
authors: P
authors: Storz
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D016023:Integrins; D017853:Phosphotransferases (Alcohol Group Acceptor); D050396:TRPP Cation Channels; C020077:1-phosphatidylinositol-4-phosphate 5-kinase