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标题文本,正文级别 1,正文级别 2,正文级别 3,正文级别 4,正文级别 5,*,标题文本,正文级别 1,正文级别 2,正文级别 3,正文级别 4,正文级别 5,*,TGF-beta/BMPsignaling pathway,By little moon,1,2,BMP,Bone morphogenetic protein,Noggin,3,TGF-beta,TGF-（transforming growth factor）,latency associated peptide（LAP）,4,Overview,LAP,TGF-beta,receptor,Smad,SBE,NATURE|VOL 390|4 DECEMBER 1997,5,latency associated peptide（LAP）,LLC into ECM,6,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 1997,7,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,8,Smads,subfamily,R-Smads,Smad,1,，,2，3,，,5，8,Co-Smad,Smad4,I-Smads,Smad6，7,9,Smads,R-Smads,receptor-activated Smads,Co-Smad,common mediator Smads,10,Regulation,Ligand,Receptor,Smad,enter nucleus,11,Ligand,理化因素,Ros,PH,temperature,生物因素,MMP2,8 protease,BMP,Noggin,12,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）,13,Smad,I-Smad(Smad 6,7),I-SmadSmurf complex,kinase or phosphatase,MAPK PPM1A,14,enter nucleus,importin-、,Ras-family GTPase,Ran-GTP,Ran-GTP,/,CAS,complex,nuclear export factor,15,cancer,CDK,（,G1 arrest,）,上皮间充质转化（,EMT,）,16,cancer,CDK,（,G1 arrest,）,上皮间充质转化（,EMT,）,17,Cell 2006 Jun 2,PPM1A Functions as a Smad Phosphatase to Terminate,TGFb Signaling,18,Cell 2006 Jun 2,19,Cell 2016 Feb 25.,20,Cell 2016 Feb 25.,21,
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