TGF-beta与BMP信号通路的相关介绍.pptVIP

TGF-beta/BMP signaling pathway By little moon BMP Bone morphogenetic protein Noggin TGF-beta TGF-β（transforming growth factor） latency associated peptide（LAP） Overview LAP TGF-beta receptor Smad SBE NATURE | VOL 390 | 4 DECEMBER 1997 latency associated peptide（LAP） LLC into ECM Receptor type II receptor Ser 213 , 409 type I receptor GS domain, Ser 165 receptor kinase The TGF beta ligand binds to a type II receptor dimer, which recruits a type I receptor dimer forming a hetero-tetrameric complex with the ligand. NATURE | VOL 390 | 4 DECEMBER 1997 Smad Domains Smad 2 Ser 465/467 R-Smad在C末端都有保守motif Ser-Ser-X-Ser，两个Ser被Receptor I磷酸化 Smads subfamily R-Smads Smad 1，2，3，5，8 Co-Smad Smad4 I-Smads Smad6，7 Smads R-Smads receptor-activated Smads Co-Smad common mediator Smads Regulation Ligand Receptor Smad enter nucleus Ligand 理化因素 Ros, PH, temperature 生物因素 MMP2,8 protease BMP Noggin Receptor BAMBI BMP and activin membrane bound inhibitor pseudo-receptor ubiquitination (lipid raft) I-Smad - Smurfs (E3泛素连接酶) endocytosis clathrin（网格蛋白） Smad I-Smad (Smad 6,7) I-Smad–Smurf complex kinase or phosphatase MAPK PPM1A enter nucleus importin-α、β Ras-family GTPase Ran-GTP Ran-GTP/CAS complex nuclear export factor cancer CDK（G1 arrest） 上皮间充质转化（EMT） cancer CDK（G1 arrest） 上皮间充质转化（EMT） Cell 2006 Jun 2 PPM1A Functions as a Smad Phosphatase to Terminate TGFb Signaling Cell 2006 Jun 2 Cell 2016 Feb 25. Cell 2016 Feb 25.