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, C2␣ and C2␤ are widely expressed in many tissues, including the epidermis, while C2␥ is confined to the liver. In contrast to the class I PI3K p110␣, which is expressed throughout the epidermis, C2␤ was found to be localized in suprabasal cells, suggesting a potential role for C2␤ in epidermal differentiation. Overexpressing C2␤ in epidermal cells in vitro induced differentiation markers. To study a role for C2␤ in tissue, we generated transgenic mice overexpressing C2␤ in both suprabasal and basal epidermal layers. These mice lacked epidermal abnormalities. Mice deficient in C2␤ were then generated by targeted gene deletion. C2␤ knockout mice were viable and fertile and displayed normal epidermal growth, differentiation, barrier function, and wound healing. To exclude compensation by C2␣, RNA interference was then used to knock down both C2␣ and C2␤ in epidermal cells simultaneously. Induction of differentiation markers was unaffected in the absence of C2␣ and C2␤. These findings indicate that class II PI3Ks are not essential for epidermal differentiation.

A distinct inflammatory gene expression profile in patients with psoriatic arthritis

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PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models

“…Body weights and food consumption were monitored 3 times weekly. Mouse genotypes were established using previously published methodology (19,20,38). Supplemental Table 1 shows all mouse lines used for this study.…”

The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function

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