Abstract

TGF-a is expressed as a transmembrane protein, and cells can release soluble TGF-a into the medium as a result of the regulated proteolytic cleavage of the ectodomain. The laboratory has identified several transmembrane and cytoplasmic proteins that interact with TM TGF-a and obtained the full-length cDNAs. The hypothesis is that these associated proteins regulate intracellular transport, maturation, cell surface presentation and ectodomain cleavage of TM TGF-a. The application has four specific aims, each focusing on a defined protein that associates with TM TGF-a.
Aim 1 will characterize the association of the tetraspan protein CD9.
Aims 2 and 3 will focus on the biochemical and functional characterization of human homologs of Drosophila Rhomboid and Cornichon.
Aim 4 focuses on the functional characterization of p59, a PDZ containing protein implicated in TM TGF-a transport through the Golgi

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054826-13
Application #
6836042
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Blair, Donald G
Project Start
1992-04-08
Project End
2005-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
13
Fiscal Year
2005
Total Cost
$300,891
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Dentistry
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Castro, Carolina Perez; Piscopo, Denise; Nakagawa, Takatoshi et al. (2007) Cornichon regulates transport and secretion of TGFalpha-related proteins in metazoan cells. J Cell Sci 120:2454-66
Nakagawa, Takatoshi; Guichard, Annabel; Castro, Carolina Perez et al. (2005) Characterization of a human rhomboid homolog, p100hRho/RHBDF1, which interacts with TGF-alpha family ligands. Dev Dyn 233:1315-31
Fan, Huizhou; Turck, Christoph W; Derynck, Rik (2003) Characterization of growth factor-induced serine phosphorylation of tumor necrosis factor-alpha converting enzyme and of an alternatively translated polypeptide. J Biol Chem 278:18617-27
Shi, W; Fan, H; Shum, L et al. (2000) The tetraspanin CD9 associates with transmembrane TGF-alpha and regulates TGF-alpha-induced EGF receptor activation and cell proliferation. J Cell Biol 148:591-602
Kuo, A; Zhong, C; Lane, W S et al. (2000) Transmembrane transforming growth factor-alpha tethers to the PDZ domain-containing, Golgi membrane-associated protein p59/GRASP55. EMBO J 19:6427-39
Miettinen, P J; Chin, J R; Shum, L et al. (1999) Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure. Nat Genet 22:69-73
Fan, H; Derynck, R (1999) Ectodomain shedding of TGF-alpha and other transmembrane proteins is induced by receptor tyrosine kinase activation and MAP kinase signaling cascades. EMBO J 18:6962-72
Kornblum, H I; Zurcher, S D; Werb, Z et al. (1999) Multiple trophic actions of heparin-binding epidermal growth factor (HB-EGF) in the central nervous system. Eur J Neurosci 11:3236-46
Kornblum, H I; Hussain, R; Wiesen, J et al. (1998) Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor. J Neurosci Res 53:697-717
Hom, Y K; Young, P; Wiesen, J F et al. (1998) Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma. Endocrinology 139:913-21

Showing the most recent 10 out of 14 publications