Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Mol Biol Cell. 2012 Mar;23(6):1129-39. doi: 10.1091/mbc.E11-12-1018. Epub 2012 Jan 25.

GARP regulates the bioavailability and activation of TGFβ.

Author information

  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Immune Disease Institute and Children's Hospital, Boston, MA 02115, USA.

Abstract

Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-β (proTGFβ) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGFβ activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGFβ1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGFβ1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGFβ-binding protein for binding to proTGFβ1. Association between GARP and proTGFβ1 prevents the secretion of TGFβ1. Integrin α(V)β(6) and to a lesser extent α(V)β(8) are able to activate TGFβ from the GARP-proTGFβ1 complex. Activation requires the RGD motif of latent TGFβ, disulfide linkage between GARP and latent TGFβ, and membrane association of GARP. Our results show that GARP is a latent TGFβ-binding protein that functions in regulating the bioavailability and activation of TGFβ.

PMID:
22278742
[PubMed - indexed for MEDLINE]
PMCID:
PMC3302739
Free PMC Article

Images from this publication.See all images (9)Free text

FIGURE 1:
FIGURE 2:
FIGURE 3:
FIGURE 4:
FIGURE 5:
FIGURE 6:
FIGURE 7:
FIGURE 8:
FIGURE 9:
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk