Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor

Science ◽  
1993 ◽  
Vol 260 (5112) ◽  
pp. 1344-1348 ◽  
Author(s):  
R Ebner ◽  
R. Chen ◽  
L Shum ◽  
S Lawler ◽  
T. Zioncheck ◽  
...  
Keyword(s):  
Type I ◽  
Type Ii ◽  
Tgf Beta ◽  
Beta Receptor

scholarly journals Plasmin cleaves betaglycan and releases a 60 kDa transforming growth factor-β complex from the cell surface

1994 ◽  
Vol 302 (1) ◽  
pp. 199-205 ◽  
Author(s):  
J Lamarre ◽  
J Vasudevan ◽  
S L Gonias
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Type I ◽  
Type Ii ◽  
Tgf Beta ◽  
Beta Receptor ◽  
Cell Extracts ◽  
Beta 2

Plasmin regulates the activity and distribution of transforming growth factor beta (TGF-beta) and other growth factors. The purpose of the present investigation was to determine the effects of plasmin on cellular receptors for TGF-beta. AKR-2B fibroblasts were affinity-labelled with 125I-TGF-beta 1 and 125I-TGF-beta 2, demonstrating betaglycan, the type-I TGF-beta receptor and the type-II TGF-beta receptor. Treatment of TGF-beta-affinity-labelled cells with plasmin (10-100 nM) for 1 h profoundly and selectively decreased recovery of TGF-beta-betaglycan complex. The type-I and type-II receptors were not plasmin substrates. A radiolabelled complex with an apparent mass of 60 kDa was detected by SDS/PAGE in both the medium and cell extracts of plasmin-treated affinity-labelled cells. In order to demonstrate that plasmin cleavage of betaglycan did not require prior exposure of the betaglycan to cross-linking agent, AKR-2B cells were treated with plasmin first and then affinity-labelled. Markedly decreased TGF-beta binding to cellular betaglycan was observed. Although plasmin treatment of AKR-2B cells decreased overall binding of 125I-TGF-beta 1 and 125I-TGF-beta 2, the rate at which the cells degraded bound 125I-TGF-beta at 37 degrees C was not changed. AKR-2B cells treated with plasmin demonstrated slightly increased [3H]thymidine incorporation; the plasmin-treated cells retained their ability to respond to TGF-beta. Conditioned medium from plasmin-treated AKR-2B cells contained increased amounts of active TGF-beta as determined in Mv 1 Lu epithelial-cell-proliferation assays. Specific cleavage of betaglycan represents a novel mechanism whereby plasmin may regulate the assortment of receptors available for TGF-beta. In addition, plasmin may facilitate transfer of active TGF-beta between neighbouring cells by releasing the active growth factor from the cell surface.

Determination of type I receptor specificity by the type II receptors for TGF-beta or activin

Science ◽  
1993 ◽  
Vol 262 (5135) ◽  
pp. 900-902 ◽  
Author(s):  
R Ebner ◽  
R. Chen ◽  
S Lawler ◽  
T Zioncheck ◽  
R Derynck
Keyword(s):  
Type I ◽  
Type Ii ◽  
Tgf Beta ◽  
Receptor Specificity

scholarly journals Two distinct transmembrane serine/threonine kinases from Drosophila melanogaster form an activin receptor complex.

1994 ◽  
Vol 14 (2) ◽  
pp. 944-950 ◽  
Author(s):  
J L Wrana ◽  
H Tran ◽  
L Attisano ◽  
K Arora ◽  
S R Childs ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Transmembrane Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Type Ii ◽  
Tgf Beta ◽  
Activin Receptor ◽  
Domain Of Unknown Function

A transmembrane protein serine/threonine kinase, Atr-I, that is structurally related to receptors for members of the transforming growth factor-beta (TGF-beta) family has been cloned from Drosophila melanogaster. The spacing of extracellular cysteines and the cytoplasmic domain of Atr-I resemble most closely those of the recently described mammalian type I receptors for TGF-beta and activin. When expressed alone in test cells, Atr-I is unable to bind TGF-beta, activin, or bone morphogenetic protein 2. However, Atr-I binds activin efficiently when coexpressed with the distantly related Drosophila activin receptor Atr-II, with which it forms a heteromeric complex. Atr-I can also bind activin in concert with mammalian activin type II receptors. Two alternative forms of Atr-I have been identified that differ in an ectodomain region encompassing the cysteine box motif characteristic of receptors in this family. Comparison of Atr-I with other type I receptors reveals the presence of a characteristic 30-amino-acid domain immediately upstream of the kinase region in all these receptors. This domain, of unknown function, contains a repeated Gly-Ser sequence and is therefore referred to as the GS domain. Maternal Atr-I transcripts are abundant in the oocyte and widespread during embryo development and in the imaginal discs of the larva. The structural properties, binding specificity, and dependence on type II receptors define Atr-I as an activin type I receptor from D. melanogaster. These results indicate that the heteromeric kinase structure is a general feature of this receptor family.

Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin

1994 ◽  
Vol 14 (6) ◽  
pp. 3810-3821
Author(s):  
J Cárcamo ◽  
F M Weis ◽  
F Ventura ◽  
R Wieser ◽  
J L Wrana ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Amino Acid Sequence Identity ◽  
Transforming Growth Factor ◽  
Type I ◽  
Type Ii ◽  
Tgf Beta ◽  
Transcriptional Responses ◽  
Receptor Complexes ◽  
Growth Inhibitory ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) and activin bind to receptor complexes that contain two distantly related transmembrane serine/threonine kinases known as receptor types I and II. The type II receptors determine ligand binding specificity, and each interacts with a distinct repertoire of type I receptors. Here we identify a new type I receptor for activin, ActR-IB, whose kinase domain is nearly identical to that of the recently cloned TGF-beta type I receptor, T beta R-I. ActR-IB has the structural and binding properties of a type I receptor: it binds activin only in the presence of an activin type II receptor and forms a heteromeric noncovalent complex with activin type II receptors. In Mv1Lu lung epithelial cells, ActR-IB and T beta R-I signal a common set of growth-inhibitory and transcriptional responses in association with their corresponding ligands and type II receptors. The transcriptional responses include elevated expression of fibronectin and plasminogen activator inhibitor 1. Although T beta R-I and ActR-IB are nearly identical in their kinase domains (90% amino acid sequence identity), their corresponding type II receptor kinase domains are very different from each other (42% amino acid sequence identity). Therefore, signaling of a specific set of responses by TGF-beta and activin correlates with the presence of similar type I kinases in their complex. Indeed, other TGF-beta and activin type I receptors (TSR-I and ActR-I) whose kinase domains significantly diverge from those of T beta R-I and ActR-IB do not substitute as mediators of these growth-inhibitory and extracellular matrix transcriptional responses. Hence, we conclude that the type I receptor subunits are primary specifiers of signals sent by TGF-beta and activin receptor complexes.

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