title: The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability.
abstract: Sterile 20 (STE20) protein kinases, which include germinal center kinases and p21-activated protein kinases, are known to activate mitogen-activated protein kinase pathways (c-Jun NH(2)-terminal kinase, p38, or extracellular signal-regulated kinase), leading to changes in gene transcription. Some STE20s can also regulate the cytoskeleton, and we have shown that the germinal center kinase-like kinase prostate-derived STE20-like kinase (PSK) affects actin cytoskeletal organization. Here, we demonstrate that PSK colocalizes with microtubules; and that this localization is disrupted by the microtubule depolymerizing agent nocodazole. The association of PSK with microtubules results in the production of stabilized perinuclear microtubule cables that are nocodazole-resistant and contain increased levels of acetylated alpha-tubulin. Kinase-defective PSK (K57A) or the C terminus of PSK (amino acids 745-1235) lacking the kinase domain are sufficient for microtubule binding and stabilization, demonstrating that the catalytic activity of the protein is not required. The localization of PSK to microtubules occurs via its C terminus, and PSK binds and phosphorylates alpha- and beta-tubulin in vitro. The N terminus of PSK (1-940) is unable to bind or stabilize microtubules, demonstrating that PSK must associate with microtubules for their reorganization to occur. These results demonstrate that PSK interacts with microtubules and affects their organization and stability independently of PSK kinase activity.
authors.affiliation: Department of Academic Surgery, GKT School of Medicine and Dentistry, Rayne Institute, 123 Coldharbour Lane, London SE5 9NU, United Kingdom.
authors.forename: Costas
authors.initials: C
authors.lastname: Mitsopoulos
authors.forename: Ceniz
authors.initials: C
authors.lastname: Zihni
authors.forename: Ritu
authors.initials: R
authors.lastname: Garg
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
authors.forename: Jonathan D H
authors.initials: JD
authors.lastname: Morris
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019556:COS Cells; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000970:Antineoplastic Agents; D011494:Protein Kinases; C404957:TAOK2 protein, human; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D017239:Paclitaxel; D015739:Nocodazole