title: The class II phosphoinositide 3-kinase C2beta 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, C2alpha and C2beta are widely expressed in many tissues, including the epidermis, while C2gamma is confined to the liver. In contrast to the class I PI3K p110alpha, which is expressed throughout the epidermis, C2beta was found to be localized in suprabasal cells, suggesting a potential role for C2beta in epidermal differentiation. Overexpressing C2beta in epidermal cells in vitro induced differentiation markers. To study a role for C2beta in tissue, we generated transgenic mice overexpressing C2beta in both suprabasal and basal epidermal layers. These mice lacked epidermal abnormalities. Mice deficient in C2beta were then generated by targeted gene deletion. C2beta knockout mice were viable and fertile and displayed normal epidermal growth, differentiation, barrier function, and wound healing. To exclude compensation by C2alpha, RNA interference was then used to knock down both C2alpha and C2beta in epidermal cells simultaneously. Induction of differentiation markers was unaffected in the absence of C2alpha and C2beta. These findings indicate that class II PI3Ks are not essential for epidermal differentiation.
authors.affiliation: Veterans Affairs Palo Alto Healthcare System, CA 94304, USA.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Harada
authors.forename: Amy B
authors.initials: AB
authors.lastname: Truong
authors.forename: Ti
authors.initials: T
authors.lastname: Cai
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D058541:Class II Phosphatidylinositol 3-Kinases; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034622:RNA Interference; D015533:Transcriptional Activation; D014945:Wound Healing / Q000235:genetics
chemical_list: D058541:Class II Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C502616:PIK3C2B protein, human