Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase

Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kina se encoded by the myotonic dystrophy (DIM) locus on human chromosome 19q13. 3. It is a close relative of other kinases that interact with members of th e Rho family of small GTPases. We show here that the actin cytoskeleton-lin ked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activate s its transphosphorylation activity in a GTP-sensitive manner. DMPK can als o 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 ne, :us for cross-talk between their respective pathways and may partially expl ain the remarkable pleiotropy of DM. (C) 2000 Federation of European Bioche mical Societies. Published by Elsevier Science B.V. All rights reserved.