PMID: 12761180May 23, 2003Paper

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

Journal of Biochemistry
Mikiko TakahashiYoshitaka Ono

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.

Citations

Jan 27, 2004·Biochemical and Biophysical Research Communications·Yusuke GotohYoshitaka Ono
May 15, 2007·Oncogene·Z G Goldsmith, D N Dhanasekaran
Nov 3, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Katsuya KajimotoJunichi Sadoshima
Mar 22, 2016·ACS Chemical Biology·Sebastian MatheaStefan Knapp
Jul 14, 2011·The Biochemical Journal·Alejandra CollazosPeter J Parker
Oct 28, 2009·The Biochemical Journal·Kazuhiro ShigaHideyuki Mukai
Apr 8, 2004·Molecular Cell·Maria Julia MarinissenJ Silvio Gutkind
Mar 26, 2005·Molecular Carcinogenesis·Takayuki IsagawaYoshitaka Ono
Jun 28, 2005·The Journal of Biological Chemistry·Rebecca A DeatonStephen R Grant
Aug 11, 2017·Scientific Reports·Rana MashudHideyuki Mukai
May 22, 2016·Molecular Cancer Therapeutics·Daniel MarkowitzRosamaria Ruggieri
Apr 15, 2020·Molecular Cell·Anna Constance VindSimon Bekker-Jensen

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