The class II phosphoinositide 3-kinase C2β is not essential for epidermal differentiation

Phosphoinositide 3-kinases (PI3Ks) regulate an array of cellular processes and are comprised of three classes. Class I PI3Ks include the well-studied agonist-sensitive p110 isoforms; however, the functions of class II and III PI3Ks are less well characterized. Of the three class II PI3Ks, C2 alpha and C2 beta are widely expressed in many tissues, including the epidermis, while C2 gamma is confined to the liver. In contrast to the class I PI3K p110 alpha, which is expressed throughout the epidermis, C2 beta was found to be localized in suprabasal cells, suggesting a potential role for C2 beta in epidermal differentiation. Overexpressing C2 beta in epidermal cells in vitro induced differentiation markers. To study a role for C2 beta in tissue, we generated transgenic mice overexpressing C2 beta in both suprabasal and basal epidermal layers. These mice lacked epidermal abnormalities. Mice deficient in C2 beta were then generated by targeted gene deletion. C2 beta knockout mice were viable and fertile and displayed normal epidermal growth, differentiation, barrier function, and wound healing. To exclude compensation by C2 alpha, RNA interference was then used to knock down both C2 alpha and C2 beta in epidermal cells simultaneously. Induction of differentiation markers was unaffected in the absence of C2 alpha and C2 beta. These findings indicate that class II PI3Ks are not essential for epidermal differentiation.