title: Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase.
abstract: Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kinase encoded by the myotonic dystrophy (DM) locus on human chromosome 19q13.3. It is a close relative of other kinases that interact with members of the Rho family of small GTPases. We show here that the actin cytoskeleton-linked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activates its transphosphorylation activity in a GTP-sensitive manner. DMPK can also bind Raf-1 kinase, the Ras-activated molecule of the MAP kinase pathway. Purified Raf-1 kinase phosphorylates and activates DMPK. The interaction of DMPK with these distinct signals suggests that it may play a role as a nexus for cross-talk between their respective pathways and may partially explain the remarkable pleiotropy of DM.
authors.affiliation: Department of Neurology, NS B302, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: E T
authors.initials: ET
authors.lastname: Walch
authors.forename: P W
authors.initials: PW
authors.lastname: Dunne
authors.forename: H F
authors.initials: HF
authors.lastname: Epstein
mesh_terms: D000818:Animals; D019556:COS Cells; D004789:Enzyme Activation; D006801:Humans; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C585517:DMPK protein, human; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D020744:rac GTP-Binding Proteins