ATF-2 Is a Common Nuclear Target of Smad and TAK1 Pathways in Transforming Growth Factor-beta Signaling Export

@article{citeulike:2800792, abstract = {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. 10.1074/jbc.274.13.8949}, author = {Sano, Yuji and Harada, Jun and Tashiro, Shigeki and Gotoh-Mandeville, Ryoko and Maekawa, Toshio and Ishii, Shunsuke}, citeulike-article-id = {2800792}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.274.13.8949}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/274/13/8949}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/10085140}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=10085140}, day = {26}, doi = {10.1074/jbc.274.13.8949}, journal = {J. Biol. Chem.}, keywords = {atf, creb}, month = {March}, number = {13}, pages = {8949--8957}, posted-at = {2008-05-15 07:09:23}, priority = {2}, title = {ATF-2 Is a Common Nuclear Target of Smad and TAK1 Pathways in Transforming Growth Factor-beta Signaling}, url = {http://dx.doi.org/10.1074/jbc.274.13.8949}, volume = {274}, year = {1999} }

TY - JOUR ID - citeulike:2800792 L3 - citeulike-article-id:2800792 N2 - 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. 10.1074/jbc.274.13.8949 IS - 13 JF - J. Biol. Chem. EP - 8957 TI - ATF-2 Is a Common Nuclear Target of Smad and TAK1 Pathways in Transforming Growth Factor-beta Signaling VL - 274 SP - 8949 KW - atf KW - creb AU - Sano, Yuji AU - Harada, Jun AU - Tashiro, Shigeki AU - Gotoh-Mandeville, Ryoko AU - Maekawa, Toshio AU - Ishii, Shunsuke PY - 1999/03/26/ UR - http://dx.doi.org/10.1074/jbc.274.13.8949 ER -