*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 10542228


    		J Biol Chem. 1999 Nov 5;274(45):31981-6.
     
			The role of DOC-2/DAB2 protein phosphorylation
			in the inhibition of AP-1 activity. An underlying
			mechanism of its tumor-suppressive function
			in prostate cancer.

			Tseng CP(1), Ely BD, Pong RC, Wang Z, Zhou
			J, Hsieh JT.

			Author Information
			(1) Department of Urology,
			University of Texas Southwestern Medical Center,
			Dallas, Texas 75235-9110, USA.

			DOC-2/DAB2, a novel phosphoprotein with signal-transducing
			capability, inhibits human prostatic cancer
			cells (Tseng, C.-P., Ely, B. D., Li, Y.,
			Pong, R.-C., and Hsieh, J.-T. (1998) Endocrinology
			139, 3542-3553). However, its mechanism
			of action is not understood completely.
			This study delineates the functional significance
			of DOC-2/DAB2 protein phosphorylation and
			demonstrates that in vivo activation of
			protein kinase C (PKC) by
			12-O-tetradecanoylphorbol-13-acetate (TPA)
			induces DOC-2/DAB2 phosphorylation, including
			a serine residue at position 24. Mutation
			of Ser(24) to Ala reduced DOC-2/DAB2 phosphorylation
			by PKC. Using a synthetic Ser(24) peptide
			(APS(24)KKEKKKGSEKTD) or recombinant DOC-2/DAB2
			as substrates, PKCbetaII, PKCgamma, and
			PKCdelta (but not casein kinase II) directly
			phosphorylated Ser(24) in vitro. This indicates
			that DOC-2/DAB2 is a PKC-specific substrate.
			Since expression of wild-type DOC-2/DAB2,
			but not the S24A mutant, inhibited TPA-induced
			AP-1 activity in prostatic epithelial cells,
			phosphorylation of Ser(24) appears to play
			a critical role in modulating TPA-induced
			AP-1 activity. Taken together, these data
			suggest that PKC-regulated phosphorylation
			of DOC-2/DAB2 protein may help its growth
			inhibitory function.

			PMID: 10542228 [Indexed for MEDLINE]

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