TGF-beta与BMP信号通路的相关介绍.ppt

1、1,TGF-beta/BMPsignaling pathway,By little moon,2,3,BMP,Bone morphogenetic protein Noggin,4,TGF-beta,TGF-（transforming growth factor） latency associated peptide（LAP）,5,Overview,LAP TGF-beta receptor Smad SBE,NATURE | VOL 390 | 4 DECEMBER 1997,6,latency associated peptide（LAP）,LLC into ECM,7,Receptor,

2、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 1997,8,Smad Domains,Smad 2 Ser 465/467,R-

3、Smad在C末端都有保守motif Ser-Ser-X-Ser，两个Ser被Receptor I磷酸化,9,Smads,subfamily R-Smads Smad 1，2，3，5，8 Co-Smad Smad4 I-Smads Smad6，7,10,Smads,R-Smads receptor-activated Smads Co-Smad common mediator Smads,11,Regulation,Ligand Receptor Smad enter nucleus,12,Ligand,理化因素 Ros, PH, temperature 生物因素 MMP2,8 protease

4、 BMP Noggin,13,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）,14,Smad,I-Smad (Smad 6,7) I-SmadSmurf complex kinase or phosphatase MAPK PPM1A,15,enter nucleus,importin-、 Ras-family GTPase Ran-GTP Ran-GTP/CAS complex nuclear export factor,16,cancer,CDK（G1 arrest） 上皮间充质转化（EMT）,17,cancer,CDK（G1 arrest） 上皮间充质转化（EMT）,18,Cell 2006 Jun 2,PPM1A Functions as a Smad Phosphatase to Terminate TGF