title: Cdc42 is involved in PKCepsilon- and delta-induced neurite outgrowth and stress fibre dismantling.
abstract: We have shown that protein kinase C (PKC)epsilon, independently of the catalytic domain, induces outgrowth of cellular processes via its regulatory domain in both neural cells and fibroblasts. This was accompanied by stress fibre loss. Here, we have examined the role of the small GTPases, Rac1, and Cdc42, in these PKC-mediated morphological and cytoskeletal changes. Both constitutively active and dominant negative Rac1 and Cdc42 attenuated the PKC-mediated outgrowth of processes. The suppression was larger for Cdc42 than for Rac1. The PKC-mediated dismantling of the stress fibres in both HiB5 and fibroblasts was inhibited by the expression of the Cdc42 mutants whereas they had smaller effects on the stress fibre dismantling induced by the ROCK inhibitor, Y-27632, indicating a more crucial role for Cdc42 in the PKC-mediated pathway. We conclude that Cdc42 is an important downstream factor in the pathway through which PKC mediates morphological and cytoskeletal effects.
authors.affiliation: Lund University, Department of Laboratory Medicine, Molecular Medicine, Entrance 78, 3rd floor, Malmö University Hospital, SE-205 02 Malmö, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Trollér
authors.forename: Christer
authors.initials: C
authors.lastname: Larsson
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000737:chemistry*; D051744:Protein Kinase C-epsilon / Q000737:chemistry*; D011725:Pyridines / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000737:chemistry / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000737:chemistry
chemical_list: D000577:Amides; D011725:Pyridines; C108830:Y 27632; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein