Ubiquitin-dependent degradation of the Smad complex terminates BMP2 signalling Ubiquitin-dependent degradation controls basal levels of R-Smad1/5/8 PathwayStep5440 PathwayStep5436 PathwayStep5435 PathwayStep5438 PathwayStep5437 PathwayStep5439 PathwayStep5434 PathwayStep5433 PathwayStep5432 PathwayStep5431 PathwayStep5430 PathwayStep5428 PathwayStep5429 PathwayStep5426 PathwayStep5427 I-Smad competes with R-Smad1/5/8 for type I receptor SKI complexes with the Smad complex, suppressing BMP2 signalling The phospho-R-Smad1/5/8:Co-Smad transfers to the nucleus Phospho-R-Smad1/5/8 forms a complex with Co-Smad I-Smad competes with Co-Smad for R-Smad1/5/8 Phospho-R-Smad1/5/8 dissociates from the receptor complex Activated type I receptor phosphorylates R-Smad1/5/8 directly I-Smad binds to type I receptor, preventing Smad1/5/8 from being activated An anchoring protein, Endofin, recruits R-Smad1/5/8 Type II receptor phosphorylates type I receptor BMP2 binds to the receptor complex Formation of a heteromeric BMP receptor complex The ligand trap binds the ligand BMP2, blocking BMP signalling Signaling by BMP Authored: Huminiecki, L, Moustakas, A, 2007-11-07 10:22:00 GENE ONTOLOGYGO:0030509 Pubmed15621726 Reactome Database ID Release 43201451 Reactome, http://www.reactome.org ReactomeREACT_12034 Reviewed: Heldin, CH, 2007--1-1- The TGF-beta/BMP (bone morphogenetic protein) pathway incorporates several signalling pathways that share most, but not all, components of a central signal transduction engine. The general signalling scheme is rather simple: upon binding of a ligand, an activated plasma membrane receptor complex is formed, which passes on the signal towards the nucleus through a phosphorylated receptor-activated SMAD (r-SMAD). In the nucleus, the activated r-SMAD promotes transcription in a complex with a closely-related helper molecule termed the Co-SMAD. However, this simple linear pathway expands into a network when various regulatory components and mechanisms are taken into account. The signalling pathway includes a great variety of different TGF-beta/BMP superfamily ligands and receptors, several types of the r-SMAD, and functionally critical negative feedback loops. The r-SMAD/Co-SMAD can interact with a great number of transcriptional co-activators/co-repressors to regulate positively or negatively effector genes, so that the interpretation of a signal depends on the cell-type and cross talk with other signalling pathways such as Notch, MAPK and Wnt. The pathway plays a number of different biological roles in the control of embryonic and adult cell proliferation and differentiation, and it is implicated in a great number of human diseases.