title: Hydrophobic motif phosphorylation coordinates activity and polar localization of the Neurospora crassa nuclear Dbf2-related kinase COT1.
abstract: Nuclear Dbf2p-related (NDR) kinases and associated proteins are recognized as a conserved network that regulates eukaryotic cell polarity. NDR kinases require association with MOB adaptor proteins and phosphorylation of two conserved residues in the activation segment and hydrophobic motif for activity and function. We demonstrate that the Neurospora crassa NDR kinase COT1 forms inactive dimers via a conserved N-terminal extension, which is also required for the interaction of the kinase with MOB2 to generate heterocomplexes with basal activity. Basal kinase activity also requires autophosphorylation of the COT1-MOB2 complex in the activation segment, while hydrophobic motif phosphorylation of COT1 by the germinal center kinase POD6 fully activates COT1 through induction of a conformational change. Hydrophobic motif phosphorylation is also required for plasma membrane association of the COT1-MOB2 complex. MOB2 further restricts the membrane-associated kinase complex to the hyphal apex to promote polar cell growth. These data support an integrated mechanism of NDR kinase regulation in vivo, in which kinase activation and cellular localization of COT1 are coordinated by dual phosphorylation and interaction with MOB2.
authors.affiliation: Institute for Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Maerz
authors.forename: Anne
authors.initials: A
authors.lastname: Dettmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Seiler
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000201:enzymology*; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D009492:Neurospora crassa / Q000201:enzymology* / Q000648:ultrastructure; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D005656:Fungal Proteins; D017346:Protein Serine-Threonine Kinases