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Regulation of integrin activation by calcineurin

Institution: Scripps Research Institute
Investigator(s): Kayoko Kimbara, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11FT-0111 Award: $68,437
Subject Area: Cardiovascular Disease
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
Cardiovascular disease is one major consequence of excessive tobacco use. Blood cells are recruited to the lesions of blood vessels resulting from smoking. These cells may eventually undergo extensive physiological changes that lead to clot formation. A group of proteins on cell surface, known as integrin, facilitate the recruitment of blood cells. Integrin determines the "stickiness" of a cell and also how fast a cell moves. Integrins thus represents attractive target molecules for therapeutic manipulation of blood cells. Thus, it is of great importance to clearly understand how the biological function of integrin is controlled, which is now the objective of my proposal.

This proposal focuses on one type of integrin, namely alpha 4 integrin, which like all other integrins, has a large extracellular domain on the outside of cell surface and a short tail on the inside of cell membrane. While the large extracellular domain binds to surface proteins presented from neighboring cells, the short tail makes connections to proteins inside a cell. Through such connections, alpha 4 integrin sends off signals deep into a cell who will then respond to these signals by altering its "behavior". We previously found that its connections to proteins inside a cell are severed when the short tail of alpha4 integrin is modified in the form of addition of a chemical group called "phosphate". My objective is to identify enzyme(s) that catalyze the addition of this chemical group, plus enzymes that conversely remove such a modification.

This proposal will reveal a biological circuit that controls the movement of cells. The knowledge garnered from the study will help to identify novel targets for which drugs can be designed to hamper cardiovascular diseases.

Ras GTPases, integrins' friends or foes?
Periodical: Nature Reviews, Molecular Cell Biology Index Medicus:
Authors: Kinbara K, Goldfinger LE, Hansen M, Chou FL and Ginsberg MH ART
Yr: 0 Vol: Nbr: Abs: Pg: