TGF-beta receptor: Difference between revisions

(9 intermediate revisions by 2 users not shown)

Line 1:

__TOC__

== Function ==

'''TGF-β receptors''' (Transforming Growth Factor) (~~TGFBR~~) 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 ~~TGFBR~~:

'''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:

*'''~~TGFBR~~ I''' forms heteromeric complex with ~~TGFBR~~ II when it is bound to TGF-β. The complex transduces the TGF-β signal from the cell surface to the cytoplasm by phosphorylating proteins which regulate the transcription of genes related to cell proliferation. ~~TGFBR~~ I has high affinity for TGF-β1 and low affinity for TGF-β2.

*'''TGFR I''' forms heteromeric complex with TGFR II when it is bound to TGF-β. The complex transduces the TGF-β signal from the cell surface to the cytoplasm by phosphorylating proteins which regulate the transcription of genes related to cell proliferation. TGFR I has high affinity for TGF-β1 and low affinity for TGF-β2.

*'''~~TGFBR~~ II''' is a tumor suppressor transmembrane protein. ~~TGFBR~~ II has high affinity for TGF-β1 and low affinity for TGF-β2.

*'''TGFR II''' is a tumor suppressor transmembrane protein. TGFR II has high affinity for TGF-β1 and low affinity for TGF-β2.

*'''~~TGFBR~~ III''' is a cell-surface chondroitin sulfate / heparin sulfate proteoglycan. It acts as a reservoir of ligand for ~~TGFBRs~~. ~~TGFBR~~ 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.

See also [[Receptor]], [[TGF beta signaling pathway]], and [[Growth factors]].

== Disease ==

Over-expression of TGF causes kidney disease, diabetes and renal disease. Mutations in ~~TGFBR~~ II cause various types of tumors<ref>PMID:23884466</ref>.

Over-expression of TGF causes kidney disease, diabetes and renal disease. Mutations in TGFR II cause various types of tumors<ref>PMID:23884466</ref>.

== Structural highlights ==

~~TGFBR~~ structure contains a 100-140 residues ligand-binding N-terminal extracellular domain; a transmembrane domain; a 350-400 amino acid cytoplasmic kinase domain; and a C-terminal zona pellucida (ZP) domain of ca 260 residues which has a role in protein polymerization.

TGFR structure contains a 100-140 residues ligand-binding N-terminal extracellular domain; a transmembrane domain; a 350-400 amino acid cytoplasmic kinase domain; and a C-terminal zona pellucida (ZP) domain of ca 260 residues which has a role in protein polymerization.

== 3D Structures of TGF-beta receptor==

[[TGF-beta receptor 3D structures]]

</StructureSection>

~~== 3D Structures of TGF-β receptor==~~

~~Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}~~

~~{{#tree:id=OrganizedByTopic|openlevels=0|~~

* TGF-β receptor I; kinase domain 200-503

**[[1ias]], [[5e8s]] – hTGFBR-I kinase domain – human

**[[5e8t]], [[5e8u]] – hTGFBR-I kinase domain (mutant)

**[[5e8w]], [[5e8x]] – hTGFBR-I kinase domain (mutant) + staurosporine

**[[5e8z]] – hTGFBR-I kinase domain (mutant) + inhibitor

**[[2l5s]] – hTGFBR-I extracellular domain - NMR

**[[1b6c]] – hTGFBR-I kinase domain + FKBP12

**[[1py5]], [[3faa]], [[3gxl]], [[3hmm]], [[2wot]], [[2wou]], [[3kcf]], [[2x7o]], [[3tzm]], [[4x0m]], [[4x2j]], [[4x2k]], [[4x2n]] – hTGFBR-I kinase domain + inhibitor

**[[1vjy]] – hTGFBR-I residues 1-303 + inhibitor

**[[5usq]] – hTGFBR-I residues 123-421 + inhibitor

**[[1rw8]] – hTGFBR-I truncated kinase domain + inhibitor

* TGF-β receptor II

**[[1m9z]] – hTGFBR-II extracellular domain

**[[1plo]], [[4p7u]] – hTGFBR-II extracellular domain (mutant) - NMR

**[[5e8v]] – hTGFBR-II kinase domain (mutant)

**[[5e8y]] – hTGFBR-II kinase domain (mutant) + staurosporine

**[[5e92]] – hTGFBR-II kinase domain (mutant) + AMPPNP

**[[1ks6]] – cTGFBR-II extracellular domain - chicken

**[[1ktz]] – hTGFBR-II extracellular domain + TGF-β3

**[[5ty4]] – hTGFBR-II extracellular domain + mmTGF-β2

**[[5tx4]] – mTGFBR-II extracellular domain (mutant) + hTGF-β2 - mouse

* TGF-β receptor III

**[[3qw9]] – TGFBR-III ZP-C domain - rat

**[[4ajv]] – mTGFBR-III ZP-C domain

* TGF-β receptor I+II

**[[2pjy]] – hTGFBR-I extracellular domain (mutant) + hTGFBR-II extracellular domain (mutant) + TGF-β3

**[[3kfd]] – hTGFBR-I extracellular domain + hTGFBR-II extracellular domain + TGF-β1

}}

== References ==

[[Category:Topic Page]]

TGF-beta receptor: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-<StructureSection load='1ktz' size='340' side='right' caption='Human hTGFBR-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=''>
 __TOC__
 == Function ==
-'''TGF-β receptors''' (Transforming Growth Factor) (TGFBR) 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 TGFBR:     <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 />
-*'''TGFBR I''' forms heteromeric complex with TGFBR II when it is bound to TGF-β.  The complex transduces the TGF-β signal from the cell surface to the cytoplasm by phosphorylating proteins which regulate the transcription of genes related to cell proliferation.  TGFBR I has high affinity for TGF-β1 and low affinity for TGF-β2. <br />
+*'''TGFR I''' forms heteromeric complex with TGFR II when it is bound to TGF-β.  The complex transduces the TGF-β signal from the cell surface to the cytoplasm by phosphorylating proteins which regulate the transcription of genes related to cell proliferation.  TGFR I has high affinity for TGF-β1 and low affinity for TGF-β2. <br />
-*'''TGFBR II''' is a tumor suppressor transmembrane protein.  TGFBR II has high affinity for TGF-β1 and low affinity for TGF-β2. <br />
+*'''TGFR II''' is a tumor suppressor transmembrane protein.  TGFR II has high affinity for TGF-β1 and low affinity for TGF-β2. <br />
-*'''TGFBR III''' is a cell-surface chondroitin sulfate / heparin sulfate proteoglycan.  It acts as a reservoir of ligand for TGFBRs.  TGFBR 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.
+See also [[Receptor]], [[TGF beta signaling pathway]], and [[Growth factors]].
 == Disease ==
-Over-expression of TGF causes kidney disease, diabetes and renal disease.  Mutations in TGFBR II cause various types of tumors<ref>PMID:23884466</ref>.
+Over-expression of TGF causes kidney disease, diabetes and renal disease.  Mutations in TGFR II cause various types of tumors<ref>PMID:23884466</ref>.
 == Structural highlights ==
-TGFBR structure contains a 100-140 residues ligand-binding N-terminal extracellular domain; a transmembrane domain;  a 350-400 amino acid cytoplasmic kinase domain; and a C-terminal zona pellucida (ZP) domain of ca 260 residues which has a role in protein polymerization.
+TGFR structure contains a 100-140 residues ligand-binding N-terminal extracellular domain; a transmembrane domain;  a 350-400 amino acid cytoplasmic kinase domain; and a C-terminal zona pellucida (ZP) domain of ca 260 residues which has a role in protein polymerization.
+== 3D Structures of TGF-beta receptor==
+[[TGF-beta receptor 3D structures]]
 </StructureSection>
-== 3D Structures of TGF-β receptor==
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-{{#tree:id=OrganizedByTopic|openlevels=0|
-* TGF-β receptor I; kinase domain 200-503
-**[[1ias]], [[5e8s]] – hTGFBR-I kinase domain – human  <br />
-**[[5e8t]], [[5e8u]] – hTGFBR-I kinase domain (mutant) <br />
-**[[5e8w]], [[5e8x]] – hTGFBR-I kinase domain (mutant) + staurosporine<br />
-**[[5e8z]] – hTGFBR-I kinase domain (mutant) + inhibitor<br />
-**[[2l5s]] – hTGFBR-I extracellular domain - NMR<br />
-**[[1b6c]] – hTGFBR-I kinase domain + FKBP12 <br />
-**[[1py5]], [[3faa]], [[3gxl]], [[3hmm]], [[2wot]], [[2wou]], [[3kcf]], [[2x7o]], [[3tzm]], [[4x0m]], [[4x2j]], [[4x2k]], [[4x2n]] – hTGFBR-I kinase domain + inhibitor  <br />
-**[[1vjy]] – hTGFBR-I residues 1-303 + inhibitor  <br />
-**[[5usq]] – hTGFBR-I residues 123-421 + inhibitor  <br />
-**[[1rw8]] – hTGFBR-I truncated kinase domain + inhibitor  <br />
-* TGF-β receptor II
-**[[1m9z]] – hTGFBR-II extracellular domain <br />
-**[[1plo]], [[4p7u]] – hTGFBR-II extracellular domain (mutant) - NMR<br />
-**[[5e8v]] – hTGFBR-II kinase domain (mutant) <br />
-**[[5e8y]] – hTGFBR-II kinase domain (mutant) + staurosporine<br />
-**[[5e92]] – hTGFBR-II kinase domain (mutant) + AMPPNP<br />
-**[[1ks6]] – cTGFBR-II extracellular domain - chicken<br />
-**[[1ktz]] – hTGFBR-II extracellular domain + TGF-β3  <br />
-**[[5ty4]] – hTGFBR-II extracellular domain + mmTGF-β2  <br />
-**[[5tx4]] – mTGFBR-II extracellular domain (mutant) + hTGF-β2 - mouse<br />
-* TGF-β receptor III
-**[[3qw9]] – TGFBR-III ZP-C domain - rat<br />
-**[[4ajv]] – mTGFBR-III ZP-C domain <br />
-* TGF-β receptor I+II
-**[[2pjy]] – hTGFBR-I extracellular domain (mutant) +  hTGFBR-II extracellular domain (mutant) + TGF-β3  <br />
-**[[3kfd]] – hTGFBR-I extracellular domain +  hTGFBR-II extracellular domain + TGF-β1  <br />
-}}
 == References ==
 <references/>
 [[Category:Topic Page]]