Protein serine/threonine phosphatase PPM1A dephosphorylates Smad1 in the bone morphogenetic protein signaling pathway.
Bone morphogenetic proteins (BMPs) are secreted polypeptides belonging to the transforming growth factor-beta (TGF-beta) superfamily that activates a broad range of biological responses in the metazoan organism. The BMP-initiated signaling pathway is under tight control by processes including regulation of the ligands, the receptors, and the key downstream intracellular effector Smads. A critical point of control in BMP signaling is the phosphorylation of Smad1, Smad5, and Smad8 in their C-terminal SXS motif. Although such phosphorylation, which is mediated by the type I BMP receptor kinases in response to BMP stimulation, is well characterized, biochemical mechanisms underlying Smad dephosphorylation remain to be elucidated. In this study, we have found that PPM1A, a metal ion-dependent protein serine/threonine phosphatase, physically interacts with and dephosphorylates Smad1 both in vitro and in vivo. Functionally, overexpression of PPM1A abolishes BMP-induced transcriptional responses, whereas RNA interference-mediated knockdown of PPM1A enhances BMP signaling. Collectively, our study suggests that PPM1A plays an important role in controlling BMP signaling through catalyzing Smad dephosphorylation.
Duan
Xueyan
X
Department of Molecular and Cellular Biology, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Liang
Yao-Yun
YY
Feng
Xin-Hua
XH
Lin
Xia
X
D020816:Amino Acid Motifs; D000818:Animals; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002384:Catalysis; D002460:Cell Line; D006801:Humans; D047468:Immunoprecipitation; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D000071636:Protein Phosphatase 2C; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D051898:Smad1 Protein; D016212:Transforming Growth Factor beta; C000607456:PPM1A protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C