Targeting Human Rhomboid Family-1 Gene RHBDF 1 in Breast Cancer
Abstract
Epidermal growth factor receptor (EGFR) can be transactivated by ligands of G protein-coupled receptors (GPCR). GPCR signaling pathways often involve the formation of clathrin-coated endosomes, which interact with endoplasmic reticulum/Golgi complex to form recycling endosome and secretion vesicles containing EGFR pro-ligands such as pro-TGFalpha, which is proteolytically processed and released on the cell surface to activate EGFR in an autocrine manner. We showed previously that human rhomboid family-1 gene RHBDF1 is essential for GPCREGFR transactivation by assisting the secretion of TGF , a ligand of EGFR. We show here silencing the RHBDF1 gene with shRNA leads to inhibition of ligand-dependent activation of EGFR induced by GPCR ligands such as gastrin release peptide (GRP) and sphingosine-1-phosphate. Our findings are consistent with the view that, in response to GPCR activation, RHBDF1 critically assists pro-TGF movement to the cell surface through clathrin coated membrane trafficking.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2010
- Accession Number
- ADA562127
Entities
People
- Luyuan Li
Organizations
- University of Pittsburgh