TGF beta signaling pathway: Difference between revisions
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<StructureSection load='1ktz' size='340' side='right' caption='Human hTGFR-II extracellular domain (green) complex with TGF-β3 (grey) (PDB code [[1ktz]])' scene=''> | <StructureSection load='1ktz' size='340' side='right' caption='Human hTGFR-II extracellular domain (green) complex with TGF-β3 (grey) (PDB code [[1ktz]])' scene=''> | ||
The TGFbeta signalling pathway has an impact on a variety of cellular processes including cell proliferation, differentiation, apoptosis, growth, development, adhesion, neuronal growth, immune surveillance, tissue homeostasis and many others. Moreover, dysregulation of the normal functioning of any element is associated with pathological conditions, such as autoimmune and inflammatory diseases, cancer and cardiovascular diseases. | |||
TGFbeta superfamily ligands transduce their signals by binding and bringing together two single-pass transmembrane receptor serine/threonine kinases called type I and II receptors. This allows the phosphorylation and activation of type I receptor by type II receptor. Once type I receptor is activated propagates the signal by phosphorylating Smad proteins, which form a heterotrimeric complex. Those complexes are then translocated into the nucleus where, in conjunction with other nuclear cofactors, regulate the transcription of target genes. | |||
==The TGF beta superfamily of ligands== | ==The TGF beta superfamily of ligands== | ||
<scene name='41/416407/Tgfbeta-1/1'> TGFβ Superfamily of cytokines</scene> | |||
The TGFbeta superfamily of cytokines can be divided in two major ligand subfamilies by sequence similarities. On one hand TGFbeta/Inhibin/Nodal/Activin subfamily and on the other hand BMP (Bone Morphogenetic Protein)/AMH (Anti-Müllerian Hormone)/GDF (Growth and Differentiation Factor) subfamily. As shown here <scene name='41/416407/Tgfbeta-bmp7/1'>TgF beta in comparison with BMP-7</scene> , the members of the superfamily share a high conserved 3D structure. | |||
''' TGFβ isoforms''': <scene name='41/416407/Dimer_tgf_beta/1'>TgF beta dimer</scene>. | |||
===Bone morphogenetic protein=== | ===Bone morphogenetic protein=== | ||
[[Bone morphogenetic protein]] | [[Bone morphogenetic protein]] | ||
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[[Bone morphogenetic protein 3D structures]] | [[Bone morphogenetic protein 3D structures]] | ||
===Growth differentiation factor=== | |||
[[Growth differentiation factor]] includes mentioned above [[Bone morphogenetic protein 9]] | |||
[[Group:MUZIC:Myostatin]] | |||
===Activin=== | |||
[[Activin]] | |||
'''Activin A''' or '''inhibitin β chain A''' (ActA) is a member of the TGF-β superfamily that inhibits the proliferation of breast cancer cells. Activin interacts with activin receptors to induce phosphorylation of intracellular signalling molecules which regulate the transcription of many genes in a cell- and tissue-specific manner<ref>PMID:16140969</ref>. | |||
==[[TGF-beta receptor]]== | ==[[TGF-beta receptor]]== | ||
'''TGF-β receptors''' (Transforming Growth Factor) (TGFR) are serine/threonine kinase receptors. They are involved in paracrine signaling and are found in many types of tissue. TGF-β ligands include bone morphogenetic proteins, growth and initiation factors, anti-Mullerian hormone, activin, nodal TGF-β<ref>PMID:9525694</ref>. There are 3 types of TGFR: <br /> | '''TGF-β receptors''' (Transforming Growth Factor) (TGFR) are serine/threonine kinase receptors. They are involved in paracrine signaling and are found in many types of tissue. TGF-β ligands include bone morphogenetic proteins, growth and initiation factors, anti-Mullerian hormone, activin, nodal TGF-β<ref>PMID:9525694</ref>. There are 3 types of TGFR: <br /> | ||
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*'''TGFR III''' is a cell-surface chondroitin sulfate / heparin sulfate proteoglycan. It acts as a reservoir of ligand for TGFRs. TGFR III has high affinity for TGF-β1, TGF-β2 and TGF-β1.2. | *'''TGFR III''' is a cell-surface chondroitin sulfate / heparin sulfate proteoglycan. It acts as a reservoir of ligand for TGFRs. TGFR III has high affinity for TGF-β1, TGF-β2 and TGF-β1.2. | ||
==SMAD phosphorylation== | |||
There are five receptor regulated SMADs: SMAD1, SMAD2, SMAD3, SMAD5, and SMAD9 (sometimes referred to as SMAD8). There are essentially two intracellular pathways involving these R-SMADs. TGFβs, Activins, Nodals and some GDFs are mediated by SMAD2 and SMAD3, while BMPs, AMH and a few GDFs are mediated by SMAD1, SMAD5 and SMAD9. | |||
*[[1dd1]] - CRYSTAL STRUCTURE ANALYSIS OF THE SMAD4 ACTIVE FRAGMENT | |||
*[[1dev]] - CRYSTAL STRUCTURE OF SMAD2 MH2 DOMAIN BOUND TO THE SMAD-BINDING DOMAIN OF SARA | |||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||