title: Cofilin phosphorylation and actin polymerization by NRK/NESK, a member of the germinal center kinase family.
abstract: Nck-interacting kinase (NIK)-related kinase (NRK)/NIK-like embryo-specific kinase (NESK) is a protein kinase that belongs to the germinal center kinase family, and activates the c-Jun N-terminal kinase (JNK) signaling pathway. In this study, we examined the effect of NRK/NESK on actin cytoskeletal organization. Overexpression of NRK/NESK in COS7 cells induced accumulation of polymerized actin at the perinuclear. Phosphorylation of cofilin, an actin-depolymerizing factor, was increased in NRK/NESK-expressing HEK 293T cells. In addition, in vitro phosphorylation of cofilin was observed on NRK/NESK immunoprecipitates from HEK 293T cells expressing the kinase domain of NRK/NESK. The cofilin phosphorylation occurred at the serine residue of position 3 (Ser-3). Since the phosphorylation at Ser-3 inactivates the actin-depolymerizing activity of cofilin, these results suggest that NRK/NESK induces actin polymerization through cofilin phosphorylation. The cofilin phosphorylation did not appear to be mediated through activation of LIM-kinasel, a cofilin-phosphorylating kinase, or through the activation of JNK. Thus, cofilin is likely to be a direct substrate of NRK/NESK. NRK/NESK is predominantly expressed in skeletal muscle during the late stages of mouse embryogenesis. Thus, NRK/NESK may be involved in the regulation of actin cytoskeletal organization in skeletal muscle cells through cofilin phosphorylation.
authors.affiliation: Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Nakano
authors.forename: Masami
authors.initials: M
authors.lastname: Kanai-Azuma
authors.forename: Yoshiakira
authors.initials: Y
authors.lastname: Kanai
authors.forename: Kenji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Kazumori
authors.initials: K
authors.lastname: Yazaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Naomi
authors.initials: N
authors.lastname: Kitamura
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001704:Biopolymers / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D018858:Germinal Center / Q000378:metabolism; D000081410:Germinal Center Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012694:Serine / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D001704:Biopolymers; D000081410:Germinal Center Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D012694:Serine; D011494:Protein Kinases; C411848:Nik related kinase; D017346:Protein Serine-Threonine Kinases