The Class II Phosphoinositide 3-Kinase C2β Is Not Essential for Epidermal Differentiation

Abstract

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, C2α and C2β are widely expressed in many tissues, including the epidermis, while C2γ is confined to the liver. In contrast to the class I PI3K p110α, which is expressed throughout the epidermis, C2β was found to be localized in suprabasal cells, suggesting a potential role for C2β in epidermal differentiation. Overexpressing C2β in epidermal cells in vitro induced differentiation markers. To study a role for C2β in tissue, we generated transgenic mice overexpressing C2β in both suprabasal and basal epidermal layers. These mice lacked epidermal abnormalities. Mice deficient in C2β were then generated by targeted gene deletion. C2β knockout mice were viable and fertile and displayed normal epidermal growth, differentiation, barrier function, and wound healing. To exclude compensation by C2α, RNA interference was then used to knock down both C2α and C2β in epidermal cells simultaneously. Induction of differentiation markers was unaffected in the absence of C2α and C2β. These findings indicate that class II PI3Ks are not essential for epidermal differentiation.

ACKNOWLEDGMENTS

This work was supported by the U.S. Veterans Affairs Office of Research and Development and by grant no. AR43799 from the National Institute for Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health.

We thank J. Domin for generous gifts of PI3K C2α antibody and cDNA reagents and A. Oro for the protamine-Cre deleter mice.