Signal transduction pathways controlling morphogenesis and haematopoiesis

Signals controlling morphogenesis transforming growth factor p 

In Fig. 6.1 a prominent feature of the three-dimensional structure of the bone morphogenetic protein-7 (also known as osteogenic protein-1, OP-1) is shown. The structure displays a cystine-knot motif, characteristic of proteins of the TGF-P superfamily (and other growth regulators). 

BMP-2 has in common with BMP-7 and other members of the TGF-P family, a structural scaffold, consisting of a cystine-knot motif and two finger-like double-stranded P-sheets which determine the mode of dimerization. Secondary-structure differences between BMP-2 and BMP-7 account for the recognition and specific interaction with different binding partners. The crystal structure of human bone morphogenetic protein-2 is shown in Fig. 6.2. 

TGF-P proteins bind first to a type II receptor. The receptor-ligand complex then combines with a type I receptor, forming an oligomeric signalling receptor complex. Both type I and type II receptors have cytoplasmic serine/threonine kinase domains. TGF-P signalling is transmitted by the SMADs, a family of signal transducers and transcriptional activators (Fig. 6.3). 

TGF-p Cell-cycle arrest in epithelial and haematopoietic cells. Control of growth and differentiation of the mesenchyme. Wound healing. Formation of extracellular matrix. Immunosuppression 

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Signal transduction pathways controlling morphogenesis and haematopoiesis... 

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