Smad8 mediates the signaling of the ALK-2 [corrected] receptor serine kinase.
Smad proteins are critical intracellular mediators of signaling by growth and differentiation factors of the transforming growth factor beta superfamily. We have isolated a member of the Smad family, Smad8, from a rat brain cDNA library and biochemically and functionally characterized its ability to transduce signals from serine kinase receptors. In Xenopus embryo, Smad8 is able to transcriptionally activate a subset of mesoderm target genes similar to those induced by the receptor serine kinase, activin receptor-like kinase (ALK)-2. Smad8 can be specifically phosphorylated by a constitutively active ALK-2 but not the related receptor serine kinase, ALK-4. In response to signaling from ALK-2, Smad8 associates with a common regulatory molecule, Smad4, and this association leads to a synergistic effect on gene transcription. Furthermore, Smad8 is able to rescue the expression of mesoderm genes blocked by truncated ALK-2 in the embryo. These results indicate that Smad8 can function as a downstream signaling mediator of ALK-2.
Chen
Y
Y
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA 92037, USA.
Bhushan
A
A
Vale
W
W
D030201:Activin Receptors, Type I; D000818:Animals; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004625:Embryo, Nonmammalian; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051904:Smad8 Protein; D015534:Trans-Activators / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D017978:Receptors, Growth Factor; D051904:Smad8 Protein; C491622:Smad8 protein, Xenopus; D015534:Trans-Activators; D029867:Xenopus Proteins; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I