1: J Biol Chem. 2003 Jan 31;278(5):2921-7. Epub 2002 Nov 8. 

Regulation of myeloid zinc finger protein 2A transactivation activity through
phosphorylation by mitogen-activated protein kinases.

Ogawa H, Murayama A, Nagata S, Fukunaga R.

Department of Genetics B-3, Graduate School of Medicine, Osaka University, 2-2
Yamadaoka, Suita, Osaka 565-0871, Japan.

The myeloid zinc finger protein (MZF)-2 is a C(2)H(2) zinc finger transcription
factor that is expressed in myeloid cells and involved in the growth,
differentiation, and tumorigenesis of myeloid progenitors. Here we describe a
novel isoform of MZF-2, designated MZF-2A, and show that it is phosphorylated by
the mitogen-activated protein (MAP) kinases. An in vitro phosphorylation
experiment revealed that the transactivation domain (TAD) of MZF-2A was
phosphorylated strongly by extracellular signal-regulated kinase (ERK) and
phosphorylated weakly by p38 MAP kinase but not by Jun N-terminal kinase.
Experiments using "add-back" mutants showed that three serine residues
(Ser(257), Ser(275), and Ser(295)) in the TAD were phosphorylated in vitro by
ERK. In myeloid LGM-1 cells, various extracellular stimuli induced the
phosphorylation of these serine residues, which was differentially inhibited by
the protein kinase inhibitors U0126 and SB203580. Substitution of these
phosphorylation sites with alanines resulted in a strong enhancement of the
ability of MZF-2A to activate transcription in a luciferase reporter assay.
Taken together, these results indicate that MZF-2A is a novel target for the ERK
and p38 MAP kinase signaling pathways, and its transactivation activity is
negatively regulated by MAP kinase-mediated phosphorylation of the TAD.

PMID: 12427756 [PubMed - indexed for MEDLINE]


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