title: PCTK3/CDK18 regulates cell migration and adhesion by negatively modulating FAK activity.
abstract: PCTAIRE kinase 3 (PCTK3) is a member of the cyclin dependent kinase family, but its physiological function remains unknown. We previously reported that PCTK3-knockdown HEK293T cells showed actin accumulation at the leading edge, suggesting that PCTK3 is involved in the regulation of actin reorganization. In this study, we investigated the physiological function and downstream signal transduction molecules of PCTK3. PCTK3 knockdown in HEK293T cells increased cell motility and RhoA/Rho-associated kinase activity as compared with control cells. We also found that phosphorylation at residue Tyr-397 in focal adhesion kinase (FAK) was increased in PCTK3-knockdown cells. FAK phosphorylation at Tyr-397 was increased in response to fibronectin stimulation, whereas its phosphorylation was suppressed by PCTK3. In addition, excessive expression of PCTK3 led to the formation of filopodia during the early stages of cell adhesion in HeLa cells. These results indicate that PCTK3 controls actin cytoskeleton dynamics by negatively regulating the FAK/Rho signaling pathway.
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Minamijosanjima, Tokushima 770-8506, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Minamijosanjima, Tokushima 770-8506, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kawamoto
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Minamijosanjima, Tokushima 770-8506, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Minamijosanjima, Tokushima 770-8506, Japan.|Department of Bioscience and Bioindustry, Tokushima University Graduate School, Minamijosanjima, Tokushima 770-8513, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Minamijosanjima, Tokushima 770-8506, Japan.|Department of Bioscience and Bioindustry, Tokushima University Graduate School, Minamijosanjima, Tokushima 770-8513, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yuasa
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D054460:rho-Associated Kinases; D018844:Cyclin-Dependent Kinases; C089464:PCTAIRE-3 protein kinase; D020742:rhoA GTP-Binding Protein