Akt/PKB Regulates Laminin and Collagen IV Isotypes of the Basement Membrane

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-12, Vol.98 (25), p.14416-14421
• Main Authors: Li, Xiaofeng, Talts, Ulrika, Talts, Jan F., Arman, Esther, Ekblom, Peter, Lonai, Peter
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Basement Membrane - metabolism; Biological Sciences; Cell Differentiation; Cells, Cultured; Cellular biology; Cellular differentiation; CHO Cells; Collagen Type IV - genetics; Collagen Type IV - metabolism; Collagens; Cricetinae; Embryoid bodies; Insulin; Insulin - metabolism; Isotypes; Laminin - genetics; Laminin - metabolism; Membranes; Messenger RNA; Muscles - cytology; Muscles - metabolism; Mutation; Myoblasts; Protein Isoforms - metabolism; Protein-Serine-Threonine Kinases; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Receptors; Studies; Transcription, Genetic; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.251547198

Basement membranes are important for epithelial differentiation, cell survival, and normal and metastatic cell migration. Much is known about their breakdown and remodeling, yet their positive regulation is poorly understood. Our previous analysis of a fibroblast growth factor (FGF) receptor mutation raised the possibility that protein kinase B (Akt/PKB) activated by FGF is connected to the expression of certain laminin and type IV collagen isotypes. Here we test this hypothesis and demonstrate that constitutively active Akt/PKB, an important downstream element of phosphoinositide 3′-kinase signaling, induces the synthesis of laminin-1 and collagen IV isotypes and causes their translocation to the basement membrane. By using promoter-reporter constructs, we show that constitutively active phosphoinositide 3′-kinase-p110 or Akt/PKB activates, whereas dominant negative Akt/PKB inhibits, transcription of laminin β1 and collagen IV α1 in differentiating C2 myoblast- and insulin-induced Chinese hamster ovary-T cell cultures. These results suggest that Akt/PKB activated by receptor tyrosine kinases is involved in the positive regulation of basement membrane formation. The possible role of Akt/PKB-induced laminin and collagen IV synthesis in cell survival and differentiation will be discussed.