Expression of Transforming Growth Factor Type III Receptor in Vascular Endothelial Cells Increases Their Responsiveness to Transforming Growth Factor β2

Abstract

Bovine aortic endothelial cells (BAECs) express both type I and type II receptors for transforming growth factor beta (TGF beta). These cells respond to TGF beta 1 but are relatively refractory to another isoform of TGF beta, termed TGF beta 2. TGF beta s are thought to signal through receptor complexes composed of type I and/or type II receptors, both of which appear to be functional serine-threonine kinases. The TGF beta type III receptor, on the other hand, does not seem to have any direct signaling capacity. We have now stably transfected BAECs with the type III receptor cDNA. These cells displayed surface expression of the type III receptor protein, as determined by cross-linking with iodinated TGF beta 1 and immunoprecipitation with antibodies to the type III receptor protein. Transfected BAECs exhibit increased responsiveness to TGF beta 2 by several different criteria including an increase in plasminogen activator inhibitor-1 protein and inhibition of migration and proliferation. Thus, the type III receptor protein may play a role in presenting TGF beta 2 to the type II receptor and increase responsiveness to TGF beta 2 to a level comparable to that of TGF beta 1.

Expression of a dominant negative type II TGF-β receptor in mouse skin results in an increase in carcinoma incidence and an acceleration of carcinoma development

“…In transgenic mice with a targeted deletion of the TGF-b1 gene signaling through TGF-b2 and TGF-b3 is still present and similarly, overexpression of TGF-b1 could also alter the expression of TGF-b2 and TGF-b3. Because all three isoforms of TGF-b utilize the type II receptor for signal transduction (Cheifetz et al, 1990;Sankar et al, 1995), expression of a dominant negative receptor mutant suppresses signaling of all TGF-b isoforms. Thus, a phenotype evoked by disturbance of the Suppression of TGF-b signaling C Amendt et al balance of the three isoforms is avoided.…”

“…This approach has several advantages. It is possible to interfere with signal transduction of all three isotypes of TGF-b, TGF-b1, -b2, -b3 (Cheifetz et al, 1990;Sankar et al, 1995). Furthermore, the tissue speci®c expression cassette targets transgene expression to speci®c tissues.…”

Tyrosine Phosphorylation of Paxillin and Focal Adhesion Kinase during Insulin-like Growth Factor-I-stimulated Lamellipodial Advance

“…Because tyrosine phosphorylation of FAK and paxillin phosphorylation are associated with assembly of adhesion foci (14), their phosphorylations may help stabilize the advancing lamellipodia (10,11). Such a role for FAK and paxillin in lamellipodial advance could explain why FAK expression correlates with cell motility (41)(42)(43). Lamellipodial extension is also critical for growth cone migration (16), but at this time, the function of paxillin and FAK in this regard remains to be addressed.…”

Long-chain polyunsaturated fatty acids: Selected mechanisms of action on bone

“…Osteoblasts secreted TGF-β dose-dependently when TβRI and TβRII [74]. In primary fetal rat osteoblasts it has been shown that high levels of PGE 2 may increase TβRIII expression and in this way delay TGF-β-dependent activation of osteoblasts during the initial stabilization phase before cell replication and bone repair [75].…”