Fig. 8. A Role for Cdk5 and Trio in regulated secretion from pituitary endocrine cells. Cdk5 and p39 are highly expressed in the pituitary. Inhibition of Cdk5 by roscovitine results in a decrease in the ability of BaCl₂ to stimulate hormone release, in the accumulation of subplasma membrane filamentous actin and in a decrease in the ability of cortical large dense core vesicles to approach the plasma membrane or each other. Trio, a substrate for Cdk5 and Rho GEF, interacts with the cytosolic domain of PAM, a membrane protein localized to the regulated secretory pathway in pituitary endocrine cells. The ability of Trio to activate Rac is decreased following roscovitine treatment. Phosphorylation of Trio by Cdk5/p39 and local activation of Rac may play a role in coordinating the complex changes in the organization of the subplasma membrane actin cytoskeleton that must accompany regulated secretion and subsequent endocytosis (Bokoch, 2003).