Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-beta: implications for carcinogenesis. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2005

Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-beta: implications for carcinogenesis.

Résumé

Transforming growth factor-beta (TGF-beta) superfamily members signal via membrane-bound heteromeric serine-threonine kinase receptor complexes. Upon ligand-binding, receptor activation leads to phosphorylation of cytoplasmic protein substrates of the Smad family. Following phosphorylation and oligomerization, the latter move into the nucleus to act as transcription factors to regulate target gene expression. TGF-beta responses are not solely the result of the activation Smad cascade, but are highly cell-type specific and dependent upon interactions of Smad signaling with a variety of other intracellular signaling mechanisms, initiated or not by TGF-beta itself, that may either potentiate, synergize, or antagonize, the rather linear TGF-beta/Smad pathway. These include, (a), regulation of Smad activity by mitogen-activated protein kinases (MAPKs), (b), nuclear interaction of activated Smads with transcriptional cofactors, whether coactivators or corepressors, that may be themselves be regulated by diverse signaling mechanisms, and (c), negative feedback loops exerted by inhibitory Smads, transcriptional targets of the Smad cascade. This review focuses on how MAPKs modulate the outcome of Smad activation by TGF-beta, and how cross-signaling mechanisms between the Smad and MAPK pathways may take place and affect cell fate in the context of carcinogenesis.
Fichier principal
Vignette du fichier
Javelaud_Mauviel.pdf (358.52 Ko) Télécharger le fichier
Figs_Smad-MAPK.pdf (344.78 Ko) Télécharger le fichier
Loading...

Dates et versions

inserm-00147399 , version 1 (21-05-2007)

Identifiants

Citer

Delphine Javelaud, Alain Mauviel. Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-beta: implications for carcinogenesis.: Crosstalks between the MAP kinase and Smad pathways. Oncogene, 2005, 24 (37), pp.5742-50. ⟨10.1038/sj.onc.1208928⟩. ⟨inserm-00147399⟩

Collections

INSERM UNIV-PARIS7
58 Consultations
448 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More