GARP

Synonyms

Leucine Rich Repeat Containing 32, D11S833E, Garpin, Leucine-Rich Repeat-Containing Protein 32, LRRC32, Transforming Growth Factor Beta Activator LRRC32, GARP, Glycoprotein A Repetitions Predominant

Description

Transforming growth factor beta activator LRRC32 is a key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta. Able to outcompete LTBP1 for binding to LAP regulatory chain of TGF-beta. Controls activation of TGF-beta-1 (TGFB1) on the surface of activated regulatory T-cells (Tregs). Required for epithelial fusion during palate development by regulating activation of TGF-beta-3 (TGFB3).

KO Status

RenMab: Exclusive Partnership

Drug Information

Drug in clinical trials: 1
Latest Research Phase: Phase 1 Clinical

Drug Name

Code

Phase

Company

Indications

Clinical Trials

ABBV-151

MGH-8, ABBV151, AGRX-115, ARGX-115

Phase 1 Clinical

Argen-X

Solid tumours

HLX-60

HLX-60

Preclinical

Shanghai Henlius Biologics Co Ltd

Solid tumours

References


Title

Authors

Source

The GARP gene encodes a new member of the family of leucine-rich repeat-containing proteins

Ollendorff V., Noguchi T., Delapeyriere O., Birnbaum D.,

Cell Growth Differ. 5:213-219(1994)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression

Wang R., Wan Q., Kozhaya L., Fujii H., Unutmaz D.,

PLoS ONE 3:E2705-E2705(2008)

Membrane protein GARP is a receptor for latent TGF-beta on the surface of activated human Treg

Stockis J., Colau D., Coulie P.G., Lucas S.,

Eur. J. Immunol. 39:3315-3322(2009)

Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry

Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.,

J. Proteome Res. 8:651-661(2009)

GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells

Tran D.Q., Andersson J., Wang R., Ramsey H., Unutmaz D., Shevach E.M.,

Proc. Natl. Acad. Sci. U.S.A. 106:13445-13450(2009)

Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32)

Chan D.V., Somani A.K., Young A.B., Massari J.V., Ohtola J., Sugiyama H., Garaczi E., Babineau D., Cooper K.D., McCormick T.S.,

BMC Biochem. 12:27-27(2011)

GARP regulates the bioavailability and activation of TGFbeta

Wang R., Zhu J., Dong X., Shi M., Lu C., Springer T.A.,

Mol. Biol. Cell 23:1129-1139(2012)

Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor beta1 (TGF-beta1) Production in Human Regulatory T Cells

Huygens C., Lienart S., Dedobbeleer O., Stockis J., Gauthy E., Coulie P.G., Lucas S.,

J. Biol. Chem. 290:20105-20116(2015)