title: Signaling pathways regulating Dictyostelium myosin II.
abstract: Dictyostelium myosin II is a conventional, two-headed myosin that consists of two copies each of a myosin heavy chain (MHC), an essential light chain (ELC) and a regulatory light chain (RLC). The MHC is comprised of an amino-terminal motor domain, a neck region that binds the RLC and ELC and a carboxyl-terminal alpha-helical coiled-coil tail. Electrostatic interactions between the tail domains mediate the self-assembly of myosin II into bipolar filaments that are capable of interacting with actin filaments to generate a contractile force. In this review we discuss the regulation of Dictyostelium myosin II by a myosin light chain kinase (MLCK-A) that phosphorylates the RLC and increases motor activity and by MHC kinases (MHCKs) that phosphorylate the tail and prevent filament assembly. Dictyostelium may express as many as four MHCKs (MHCK A-D) consisting of an atypical alpha-kinase catalytic domain and a carboxyl-terminal WD repeat domain that targets myosin II filaments. A previously reported MHCK, termed MHC-PKC, now seems more likely to be a diacylglycerol kinase (DgkA). The relationship of the MHCKs to the larger family of alpha-kinases is discussed and key features of the structure of the alpha-kinase catalytic domain are reviewed. Potential upstream regulators of myosin II are described, including DgkA, cGMP, cAMP and PAKa, a target for Rac GTPases. Recent results point to a complex network of signaling pathways responsible for controling the activity and localization of myosin II in the cell.
authors.affiliation: Department of Biochemistry, Botterell Hall, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Marc A
authors.initials: MA
authors.lastname: De la Roche
authors.forename: Janet L
authors.initials: JL
authors.lastname: Smith
authors.forename: Venkaiah
authors.initials: V
authors.lastname: Betapudi
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Egelhoff
authors.forename: Graham P
authors.initials: GP
authors.lastname: Côté
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D018994:Myosin Light Chains / Q000737:chemistry / Q000378:metabolism; D024462:Myosin Type II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018994:Myosin Light Chains; D015800:Protozoan Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C033142:myosin-heavy-chain kinase; D024462:Myosin Type II