alpha 6 beta 4 Integrin, a Master Regulator of Expression of Integrins in Human Keratinocytes

作者：Kligys Kristina R; Wu Yvonne; Hopkinson Susan B; Kaur Surinder; Platanias Leonidas C; Jones Jonathan C R^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287(22): 17975-17984.

DOI：10.1074/jbc.M111.310458

Three major laminin and collagen-binding integrins in skin (alpha 6 beta 4, alpha 3 beta 1, and alpha 2 beta 1) are involved in keratinocyte adhesion to the dermis and dissemination of skin cells during wound healing and/or tumorigenesis. Knockdown of alpha 6 integrin in keratinocytes not only results in motility defects but also leads to decreased surface expression of the alpha 2, alpha 3, and beta 4 integrin subunits. Whereas alpha 2 integrin mRNA levels are decreased in alpha 6 integrin knockdown cells, alpha 3 and beta 4 integrin mRNAs levels are unaffected. Expression of either alpha 6 or alpha 3 integrin in alpha 6 integrin knockdown cells restores alpha 2 integrin mRNA levels. Moreover, re-expression of alpha 6 integrin increases beta 4 integrin protein at the cell surface, which results in an increase in alpha 3 integrin expression via activation of initiation factor 4E-binding protein 1. Our data indicate that the alpha 6 beta 4 integrin is a master regulator of transcription and translation of other integrin subunits and underscore its pivotal role in wound healing and cancer.

• 出版日期2012-5-25
• 单位西北大学