In humans, the 42 polypeptides of the transforming growth factor beta (TGFp) family control a wide variety of cellular responses. They play important roles in maintaining normal cellular homeostasis, including normal tumor suppression, and they play key roles in development. Over the last decade, significant effort has been directed toward understanding TGFp signaling, leading to significant insights regarding mechanisms that regulate this process. The signaling process is induced when the growth factor ligands bind to type I and type II signaling receptors on the cell surface. The various type I and type II receptors identified in human cells, of which there are seven and five, respectively, have been shown to exhibit broad specificity for subgroups of TGFp-like ligands (such as those specific for TGFp, activin, or BMPs). The overall mechanisms by which specificity is achieved and the determinants that govern specificity however have not been defined. Structural studies conducted thus far with the TGFp, activin, and BMP systems have revealed the unexpected observation that specificity is achieved not through variation in ligand-receptor contacts alone, but through variation in the overall assembly mode as well. The specific objective of this proposal is to define the overall mechanism by which the activin subgroup of ligands induces the coopera tive assembly of the activin type Ib and activin type II receptors. The findings that emerge from these studies will complement our overall understanding of how ligand-receptor specificity is achieved in the TGFp family by defining what is likely to be one of a limited number of assembly modes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
3F31GM073562-04S1
Application #
7983170
Study Section
Special Emphasis Panel (ZRG1-GGG-G (29))
Program Officer
Toliver, Adolphus
Project Start
2006-01-02
Project End
2010-10-01
Budget Start
2009-10-02
Budget End
2010-10-01
Support Year
4
Fiscal Year
2010
Total Cost
$27,386
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229