The recruitment of phosphatidylinositol 3-kinase to the E-cadherin-catenin complex at the plasma membrane is required for calcium-induced phospholipase C-gamma1 activation and human keratinocyte differentiation.
Calcium induces epidermal keratinocyte differentiation, but the mechanism is not completely understood. We have previously demonstrated that calcium-induced human keratinocyte differentiation requires an intracellular calcium rise caused by phosphatidylinositol 3-kinase (PI3K)-dependent activation of phospholipase C-gamma1. In this study we sought to identify the upstream signaling pathway necessary for calcium activation of PI3K and its subsequent activation of phospholipase C-gamma1. We found that calcium induces the recruitment of PI3K to the E-cadherin-catenin complex at the plasma membrane of human keratinocytes. Knocking-down E-cadherin, beta-catenin, or p120-catenin expression blocked calcium activation of PI3K and phospholipase C-gamma1 and calcium-induced keratinocyte differentiation. However, knocking-down gamma-catenin expression had no effect. Calcium-induced PI3K recruitment to E-cadherin stabilized by p120-catenin at the plasma membrane requires beta-catenin but not gamma-catenin. These data indicate that the recruitment of PI3K to the E-cadherin/beta-catenin/p120-catenin complex via beta-catenin at the plasma membrane is required for calcium-induced phospholipase C-gamma1 activation and, ultimately, keratinocyte differentiation.
Xie
Zhongjian
Z
Endocrine Unit, Veterans Affairs Medical Center, Northern California Institute for Research and Education and University of California, San Francisco, California 94121, USA. Zhongjian.Xie@ucsf.edu
Bikle
Daniel D
DD
D015820:Cadherins / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism*; D051177:Catenins / Q000737:chemistry*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D051185:gamma Catenin / Q000378:metabolism
D015820:Cadherins; D051177:Catenins; D034741:RNA, Small Interfering; D051176:beta Catenin; D051185:gamma Catenin; D019869:Phosphatidylinositol 3-Kinases; D051966:Phospholipase C gamma; D002118:Calcium