A specialized integrin-binding motif enables proTGF-ß2 activation by integrin αVß6 but not αVß8.
Proc Natl Acad Sci U S A
; 120(24): e2304874120, 2023 06 13.
Article
en En
| MEDLINE
| ID: mdl-37279271
ABSTRACT
Activation of latent transforming growth factor (TGF)-ß2 is incompletely understood. Unlike TGF-ß1 and ß3, the TGF-ß2 prodomain lacks a seven-residue RGDLXX (L/I) integrin-recognition motif and is thought not to be activated by integrins. Here, we report the surprising finding that TGF-ß2 contains a related but divergent 13-residue integrin-recognition motif (YTSGDQKTIKSTR) that specializes it for activation by integrin αVß6 but not αVß8. Both classes of motifs compete for the same binding site in αVß6. Multiple changes in the longer motif underlie its specificity. ProTGF-ß2 structures define interesting differences from proTGF-ß1 and the structural context for activation by αVß6. Some integrin-independent activation is also seen for proTGF-ß2 and even more so for proTGF-ß3. Our findings have important implications for therapeutics to αVß6 in clinical trials for fibrosis, in which inhibition of TGF-ß2 activation has not been anticipated.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Integrinas
/
Factor de Crecimiento Transformador beta2
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2023
Tipo del documento:
Article