( rs the critical activation signal. Tal...)UCSD researchers create roadmap to integrin activation

"Talin binding seems to be what throws the activation switch," Ginsberg said. "By adding controllable amounts of talin and the enzyme protein kinase C ?an enzyme that modifies other proteins ?we found we can get the cell to respond to certain agents that, in turn, activate platelet integrin GPIIb-IIIa."

Using a synthetic approach, the scientists engineered an integrin-activated pathway. By adding protein kinase C, talin or mutants to manipulate the system, they hope to define and map sites where known drugs work, and discover targets along the pathway for new drugs.

"If you think of these pathways as interstate highways on a map, this study now enables us to see other back roads that lead to the destination," said Ginsberg.

Talin is also critical for activation of related integrins, such as those on white blood cells. In these cells, activation of integrins is a critical step in the sticking and migration of white blood cells required for inflammation in diseases such as rheumatoid arthritis and inflammatory bowel disease.