Wnt5a promotes adhesion of human dermal fibroblasts by triggering a phosphatidylinositol-3 kinase/Akt signal.
Frizzled-3 (Fzd3), highly expressed in both the central nervous system (CNS) and skin, plays essential roles in axonal growth and guidance during the CNS development and may be involved in maintenance of skin integrity, although its ligand remains undetermined. In this study, we demonstrate that Wnt5a specifically binds to Fzd3 in vitro and triggers phosphorylation of Akt mediated by phosphatidylinositol-3 kinase (PI3K), but not that of ERK or protein kinase C, in human primary-cultured dermal fibroblasts. We have further found that such Wnt5a/Fzd3-triggered activation of the PI3K/Akt signal promotes integrin-mediated adhesion of human dermal fibroblasts to collagen I-coated dishes. Based on another finding that Wnt5a/Fzd3-triggered activation of the PI3K/Akt signal was blocked by an excess amount of a recombinant Fzd3-cysteine-rich domain (CRD), but not by that of a recombinant Fzd6-CRD, it is concluded that Wnt5a is a natural ligand of Fzd3 that triggers the PI3K/Akt signal and promotes adhesion of human dermal fibroblasts.
Kawasaki
Aya
A
Noevir-Keio Research Laboratory, Noevir Co., Ltd., 35 Shinanomachi, Tokyo 160-8582, Japan.
Torii
Kosuke
K
Yamashita
Yuki
Y
Nishizawa
Koji
K
Kanekura
Kohsuke
K
Katada
Masanori
M
Ito
Minoru
M
Nishimoto
Ikuo
I
Terashita
Kenzo
K
Aiso
Sadakazu
S
Matsuoka
Masaaki
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003545:Cysteine / Q000737:chemistry; D020405:Dermis / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051157:Frizzled Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000077191:Wortmannin