Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN.

Abstract:

:PKNalpha is a fatty acid- and Rho-activated serine/threonine protein kinase having a catalytic domain homologous to members of the protein kinase C family. Recently it was reported that PKNalpha is involved in the p38 mitogen-activated protein kinase (MAPK) signaling pathway. To date, however, how PKNalpha regulates the p38gamma MAPK signaling pathway is unclear. Here we demonstrate that PKNalpha efficiently phosphorylates MLTKalpha (MLK-like mitogen-activated protein triple kinase), which was recently identified as a MAPK kinase kinase (MAPKKK) for the p38 MAPK cascade. Phosphorylation of MLTKalpha by PKNalpha enhances its kinase activity in vitro. Expression of the kinase-negative mutant of PKNalpha inhibited the mobility shift of MLTKalpha caused by osmotic shock in SDS-PAGE. Furthermore, PKNalpha associates with each member of the p38gamma MAPK signaling pathway (p38gamma, MKK6, and MLTKalpha). These results suggest that PKNalpha functions as not only an upstream activator of MLTKalpha but also a putative scaffold protein for the p38gamma MAPK signaling pathway.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Takahashi M,Gotoh Y,Isagawa T,Nishimura T,Goyama E,Kim HS,Mukai H,Ono Y

doi

10.1093/jb/mvg022

keywords:

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

181-7

issue

2

eissn

0021-924X

issn

1756-2651

journal_volume

133

pub_type

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