title: Differential regulation of alpha6beta4 integrin by PKC isoforms in murine skin keratinocytes.
abstract: In mammalian epidermis, alpha6beta4 integrin is expressed exclusively on the basal layer localized to the hemidesmosomes, where it interacts extracellularly with the laminin-5 ligand. During differentiation, loss of alpha6beta4 is associated with keratinocyte detachment from the basement membrane and upward migration. The protein kinase C (PKC) family of isoforms participates in regulation of integrin function and is linked to skin differentiation. Exposure of primary murine keratinocytes to PKC activators specifically downregulates alpha6beta4 expression. Utilizing recombinant adenoviruses, we selectively overexpressed skin PKC isoforms in primary keratinocytes. PKCdelta and PKCzeta induced downregulation of alpha6beta4 protein expression, leading to reduced keratinocyte attachment to laminin-5 and enhanced gradual detachment from the underlying matrix. In contrast, PKCalpha upregulated alpha6beta4 protein expression, leading to increased keratinocyte attachment to laminin-5 and to the underlying matrix. Altogether, these results suggest distinct roles for specific PKC isoforms in alpha6beta4 functional regulation during the early stages of skin differentiation.
authors.affiliation: Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Addy
authors.initials: A
authors.lastname: Alt
authors.forename: Marina
authors.initials: M
authors.lastname: Gartsbein
authors.forename: Motoi
authors.initials: M
authors.lastname: Ohba
authors.forename: Toshio
authors.initials: T
authors.lastname: Kuroki
authors.forename: Tamar
authors.initials: T
authors.lastname: Tennenbaum
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D039121:Integrin alpha6beta1 / Q000378:metabolism*; D007527:Isoenzymes / Q000145:classification / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000145:classification* / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism*
chemical_list: D039121:Integrin alpha6beta1; D007527:Isoenzymes; D011493:Protein Kinase C