*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 10593981


    		J Biol Chem. 1999 Dec 17;274(51):36741-9.
     
			Phosphorylation of B-Myb regulates its
			transactivation potential and DNA binding.

			Johnson TK(1), Schweppe RE, Septer J, Lewis
			RE.

			Author Information
			(1) Eppley Institute for Research in Cancer
			and Allied Diseases, University of Nebraska
			Medical Center, Omaha, Nebraska 68198-6805,
			USA.

			The transcription factor B-Myb is a cell
			cycle-regulated phosphoprotein and a potent
			regulator of cell cycle progression. Previous
			studies demonstrated that B-Myb was phosphorylated
			at the onset of S phase, suggesting that
			it could be due to cyclin-dependent kinases.
			We identified 10 B-Myb phosphorylation sites
			by automated peptide radiosequencing of
			tryptic phosphopeptides derived from in
			vivo (32)P-labeled B-Myb. Each B-Myb phosphorylation
			site contained a phosphoserine or phosphothreonine
			followed by a proline, suggesting that this
			phosphorylation is due to a proline-directed
			kinase. Cyclin A-Cdk2 and cyclin E-Cdk2
			complexes each phosphorylated B-Myb in a
			cell-free system on the same sites as in
			intact cells. Furthermore, the ability of
			B-Myb to activate a reporter plasmid was
			enhanced by the cotransfection of cyclin
			A, whereas mutagenesis of the 10 identified
			phosphorylation sites from B-Myb blocked
			the effect of cyclin A coexpression. Additional
			analysis revealed that the effect of phosphorylation
			on B-Myb transactivation potential was enhanced
			by phosphorylation sites in its carboxyl-terminal half.
			One phosphorylation site (Ser(581)) appeared
			to negatively regulate DNA binding, as mutation
			of this site enhanced the ability of B-Myb
			to bind a Myb-binding sequence. These data
			suggest that B-Myb is a target for phosphorylation
			by cyclin-Cdk2 and that phosphorylation of
			B-Myb regulates its transcriptional activity.

			PMID: 10593981 [Indexed for MEDLINE]

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