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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Shimizu M,Wang W,Walch ET,Dunne PW,Epstein HF

doi

10.1016/s0014-5793(00)01692-6

keywords:

subject

Has Abstract

pub_date

2000-06-23 00:00:00

pages

273-7

issue

3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(00)01692-6

journal_volume

475

pub_type

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