1、TGF-beta/BMPsignaling pathwayBy little moonBMPBone morphogenetic proteinNogginTGF-betaTGF-（transforming growth factor）latency associated peptide（LAP）OverviewLAPTGF-betareceptorSmad SBE NATURE | VOL 390 | 4 DECEMBER 1997 latency associated peptide（LAP）LLC into ECMReceptortype II receptor Ser 213 , 40

2、9type I receptor GS domain, Ser 165receptor kinaseThe 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 DomainsSmad 2 Ser 465/467R-Smad在C末端都有保守motif Ser-Ser-X-Ser，兩個(gè)Ser

3、被Receptor I磷酸化SmadssubfamilyR-SmadsSmad 1，2，3，5，8Co-SmadSmad4I-SmadsSmad6，7SmadsR-Smads receptor-activated SmadsCo-Smad common mediator SmadsRegulationLigandReceptorSmadenter nucleusLigand理化因素Ros, PH, temperature生物因素MMP2,8 proteaseBMP NogginReceptorBAMBIBMP and activin membrane bound inhibitorpseudo

4、-receptorubiquitination(lipid raft) I-Smad - Smurfs (E3泛素連接酶) endocytosisclathrin（網(wǎng)格蛋白） SmadI-Smad (Smad 6,7) I-SmadSmurf complexkinase or phosphatase MAPK PPM1Aenter nucleusimportin-、Ras-family GTPaseRan-GTPRan-GTP/CAS complexnuclear export factorcancerCDK（G1 arrest）上皮間充質(zhì)轉(zhuǎn)化（EMT）cancerCDK（G1 arrest）上皮間充質(zhì)轉(zhuǎn)化（EMT） Cell 2006 Jun 2PPM1A Functions as a Smad Phosphatase to Terminat