title: Ste20-related protein kinase LOSK (SLK) controls microtubule radial array in interphase.
abstract: Interphase microtubules are organized into a radial array with centrosome in the center. This organization is a subject of cellular regulation that can be driven by protein phosphorylation. Only few protein kinases that regulate microtubule array in interphase cells have been described. Ste20-like protein kinase LOSK (SLK) was identified as a microtubule and centrosome-associated protein. In this study we have shown that the inhibition of LOSK activity by dominant-negative mutant K63R-DeltaT or by LOSK depletion with RNAi leads to unfocused microtubule arrangement. Microtubule disorganization is prominent in Vero, CV-1, and CHO-K1 cells but less distinct in HeLa cells. The effect is a result neither of microtubule stabilization nor of centrosome disruption. In cells with suppressed LOSK activity centrosomes are unable to anchor or to cap microtubules, though they keep nucleating microtubules. These centrosomes are depleted of dynactin. Vero cells overexpressing K63R-DeltaT have normal dynactin "comets" at microtubule ends and unaltered morphology of Golgi complex but are unable to polarize it at the wound edge. We conclude that protein kinase LOSK is required for radial microtubule organization and for the proper localization of Golgi complex in various cell types.
authors.affiliation: Institute of Protein Research, Russian Academy of Science, 142290 Pushchino, Moscow Region, Russian Federation.
authors.forename: Anton V
authors.initials: AV
authors.lastname: Burakov
authors.forename: Olga N
authors.initials: ON
authors.lastname: Zhapparova
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kovalenko
authors.forename: Liudmila A
authors.initials: LA
authors.lastname: Zinovkina
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Potekhina
authors.forename: Nina A
authors.initials: NA
authors.lastname: Shanina
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Weiss
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kuznetsov
authors.forename: Elena S
authors.initials: ES
authors.lastname: Nadezhdina
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D016764:Cell Polarity; D018385:Centrosome / Q000201:enzymology; D004058:Diffusion; D005799:Genes, Dominant; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D007399:Interphase; D008870:Microtubules / Q000201:enzymology*; D050505:Mutant Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D000099317:Hippo Kinases
chemical_list: D050505:Mutant Proteins; D010446:Peptide Fragments; D017346:Protein Serine-Threonine Kinases; C485733:SLK protein, human; D000099317:Hippo Kinases