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Molecular and Cellular Biology, December 2005, p. 11122-11130, Vol. 25, No. 24
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.24.11122-11130.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Class II Phosphoinositide 3-Kinase C2ß Is Not Essential for Epidermal Differentiation

Kazutoshi Harada,1,2 Amy B. Truong,1,2 Ti Cai,1,2 and Paul A. Khavari1,2*

Veterans Affairs Palo Alto Healthcare System, Palo Alto, California 94304,1 Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 943052

Received 22 August 2005/ Accepted 30 September 2005

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 C2ß 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, C2ß was found to be localized in suprabasal cells, suggesting a potential role for C2ß in epidermal differentiation. Overexpressing C2ß in epidermal cells in vitro induced differentiation markers. To study a role for C2ß in tissue, we generated transgenic mice overexpressing C2ß in both suprabasal and basal epidermal layers. These mice lacked epidermal abnormalities. Mice deficient in C2ß were then generated by targeted gene deletion. C2ß 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 C2ß in epidermal cells simultaneously. Induction of differentiation markers was unaffected in the absence of C2{alpha} and C2ß. These findings indicate that class II PI3Ks are not essential for epidermal differentiation.

* Corresponding author. Mailing address: Program in Epithelial Biology, 269 Campus Drive, Room 2145, Stanford, CA 94305. Phone: (650) 725-5266. Fax: (650) 723-8762. E-mail: khavari{at}CMGM.stanford.edu.

Molecular and Cellular Biology, December 2005, p. 11122-11130, Vol. 25, No. 24
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.24.11122-11130.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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