Identification of a C-terminal region that regulates mitogen-activated protein kinase kinase-1 cytoplasmic localization and ERK activation

The Journal of Biological Chemistry
Hyukjin ChaP S Shapiro

Abstract

The C-terminal region of mitogen-activated protein kinase kinase-1 and 2 (MKK1 and MKK2) may function in regulating interactions with upstream kinases or the magnitude and duration of ERK mitogen-activated protein kinase activity. The MKK C-terminal region contains a proline-rich region that reportedly functions in regulating interactions with the Raf-1 kinase and ERK activity. In addition, phosphorylation sites in the C terminus of MKK1 have been suggested to either sustain or attenuate MKK1 activity. To further understand how phosphorylation at the C terminus of MKK1 and protein interactions regulate MKK1 function, we have generated several MKK1 C-terminal deletion mutants and examined their function in regulating MKK1 localization, ERK protein activation, and cell growth. A deletion of C-terminal amino acids encompassing two putative alpha-helices between residues 330 and 379 caused a re-distribution of mutant MKK1 proteins to membrane compartments. Immunofluorescence analysis of MKK1 mutants revealed a loss of homogenous cytosolic distribution that is typically observed with MKK1 wild type, suggesting this region regulates MKK1 cellular localization. In contrast, MKK1 C-terminal deletion mutants localized to various sized p...Continue Reading

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Citations

Jul 9, 2010·Blood·Takashi YokoyamaTakuro Nakamura
Jun 17, 2004·Journal of Neurochemistry·Jae Hyung KooFrank L Margolis
Apr 22, 2011·Science China. Life Sciences·Hao LiangShaojun Liu
Nov 7, 2003·The Journal of Biological Chemistry·Kimberly W RainesPaul Shapiro
Jan 24, 2009·Biochemistry·Thierry O FischmannVincent S Madison
Nov 23, 2006·Biochimica Et Biophysica Acta·Yoav D Shaul, Rony Seger

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