Cell signaling by imidazoline-1 receptor candidate, IRAS, and the nischarin homologue.

IRAS transfection into Chinese hamster ovary (CHO) or pheochromocytoma (PC-12) cell lines leads to the appearance of nonadrenergic binding sites for radiolabeled-clonidine. Nischarin is the mouse homologue of IRAS. IRAS seems to be a cytosolic protein that is anchored to the intracellular side of plasma membranes by a POX domain. Previous studies of IRAS-transfected HEK293 cells, and Nischarin-transfected 3T3 cells have shown this protein can intrinsically mediate cell growth and differentiation independent of imidazoline drugs through binding to insulin receptor substrates (HEK293 cells) and fibronectin receptors (3T3 cells). Herein, a growth-arrested PC-12 cell line stably transfected with IRAS is shown to express lower basal and nerve growth factor-stimulated levels of the activated form of extracellular receptor kinase than found in a vector-only transfected control cell line treated similarly. These findings suggest that IRAS is a membrane-associated mediator of receptor signaling.