Triple Functional Domain Protein (TRIO)

The TRIO protein contains 3 functional domains: a serine/threonine kinase domain and 2 guanine nucleotide exchange factor (GEF) domains for the family of Rho-like GTPases, specific for Rac1 and RhoA, respectively. These domains suggest that this enzyme may play a key role in several signaling pathways that control cell proliferation.

Overexpression of their N-terminal GEF domains enhanced secretion from immature granules, depleting cells of secretory cargo in the absence of secretagogue. This response required GEF activity and was mimicked by kalirin/Trio substrates Rac1 and RhoG. Selective pharmacologic inhibition of endogenous GEF activity decreased secretagogue-independent release of hormone precursors, causing accumulation of product peptide in mature secretory granules.