KIBRA Activators

Chemical activators of the KIBRA protein (also known as WWC1) largely operate through distinct biochemical pathways, many of which revolve around the modulation of protein phosphorylation. Some, such as Calyculin A and Okadaic Acid, inhibit protein phosphatases like PP1 and PP2A, maintaining higher phosphorylation levels of proteins, including KIBRA, and thereby indirectly increasing its activation.

A significant number of activators, including Forskolin, Isoproterenol, 8-bromo-cAMP, Epinephrine, IBMX, and Rolipram, function through the cAMP-dependent PKA pathway. These compounds increase cAMP levels, leading to PKA activation, which can then phosphorylate and activate KIBRA. Additionally, Ionomycin and A23187 are calcium ionophores that increase intracellular calcium levels. This elevation can activate calmodulin-dependent kinases which have been shown to phosphorylate and activate KIBRA. Lastly, PMA and Bisindolylmaleimide I act on the Protein Kinase C pathway which has also been implicated in KIBRA phosphorylation and activation. These chemicals illustrate the various pathways that can modulate KIBRA activity, underscoring the protein's involvement in diverse cellular events.