*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 10085140


    		J Biol Chem. 1999 Mar 26;274(13):8949-57.
     
			ATF-2 is a common nuclear target of Smad
			and TAK1 pathways in transforming growth
			factor-beta signaling.

			Sano Y(1), Harada J, Tashiro S, Gotoh-Mandeville
			R, Maekawa T, Ishii S.

			Author Information
			(1) Laboratory of Molecular Genetics, Tsukuba
			Life Science Center, RIKEN, 3-1-1 Koyadai,
			Tsukuba, Ibaraki 305-0074, Japan.

			Upon transforming growth factor-beta (TGF-beta)
			binding to its cognate receptor, Smad3 and
			Smad4 form heterodimers and transduce the
			TGF-beta signal to the nucleus. In addition
			to the Smad pathway, another pathway involving
			a member of the mitogen-activated protein
			kinase kinase kinase family of kinases,
			TGF-beta-activated kinase-1 (TAK1), is required
			for TGF-beta signaling. However, it is unknown
			how these pathways function together to
			synergistically amplify TGF-beta signaling.
			Here we report that the transcription factor
			ATF-2 (also called CRE-BP1) is bound by
			a hetero-oligomer of Smad3 and Smad4 upon
			TGF-beta stimulation. ATF-2 is one member
			of the ATF/CREB family that binds to the
			cAMP response element, and its activity
			is enhanced after phosphorylation by
			stress-activated protein kinases such as
			c-Jun N-terminal kinase and p38. The binding
			between ATF-2 and Smad3/4 is mediated via
			the MH1 region of the Smad proteins and
			the basic leucine zipper region of ATF-2.
			TGF-beta signaling also induces the phosphorylation
			of ATF-2 via TAK1 and p38. Both of these
			actions are shown to be responsible for
			the synergistic stimulation of ATF-2
			trans-activating capacity. These results
			indicate that ATF-2 plays a central role
			in TGF-beta signaling by acting as a common
			nuclear target of both Smad and TAK1 pathways.

			PMID: 10085140 [Indexed for MEDLINE]

     			                         Tweet       Print