title: Twitchin kinase interacts with MAPKAP kinase 2 in Caenorhabditis elegans striated muscle.
abstract: In Caenorhabditis elegans, twitchin is a giant polypeptide located in muscle A-bands. The protein kinase of twitchin is autoinhibited by 45 residues upstream (NL) and 60 residues downstream (CRD) of the kinase catalytic core. Molecular dynamics simulation on a twitchin fragment revealed that the NL is released by pulling force. However, it is unclear how the CRD is removed. To identify proteins that may remove the CRD, we performed a yeast two-hybrid screen using twitchin kinase as bait. One interactor is MAK-1, C. elegans orthologue of MAPKAP kinase 2. MAPKAP kinase 2 is phosphorylated and activated by p38 MAP kinase. We demonstrate that the CRD of twitchin is important for binding to MAK-1. mak-1 is expressed in nematode body wall muscle, and antibodies to MAK-1 localize between and around Z-disk analogues and to the edge of A-bands. Whereas unc-22 mutants are completely resistant, mak-1 mutants are partially resistant to nicotine. MAK-1 can phosphorylate twitchin NL-Kin-CRD in vitro. Genetic data suggest the involvement of two other mak-1 paralogues and two orthologues of p38 MAP kinase. These results suggest that MAK-1 is an activator of twitchin kinase and that the p38 MAP kinase pathway may be involved in the regulation of twitchin.
authors: Department of Pathology, Emory University, Atlanta, GA 30322.
authors: Yohei
authors: Y
authors: Matsunaga
authors: Department of Pathology, Emory University, Atlanta, GA 30322.
authors: Hiroshi
authors: H
authors: Qadota
authors: Department of Pathology, Emory University, Atlanta, GA 30322.
authors: Miho
authors: M
authors: Furukawa
authors: Department of Pathology, Emory University, Atlanta, GA 30322.
authors: Heejoo Helen
authors: HH
authors: Choe
authors: Department of Pathology, Emory University, Atlanta, GA 30322 pathgb@emory.edu.
authors: Guy M
authors: GM
authors: Benian
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D054792:Muscle, Striated / Q000201:enzymology*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D029742:Caenorhabditis elegans Proteins; D002148:Calmodulin-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C489233:unc-22 protein, C elegans; C000605621:MAK-1 protein, C elegans