IQGAP1 regulates hyaluronan-mediated fibroblast motility and proliferation.
IQGAP1, an essential scaffolding protein, forms a complex with the hyaluronan receptor CD44. In this study, we have examined the importance of IQGAP1 for hyaluronan-mediated fibroblast migration and proliferation. Hyaluronan induced formation of F-actin fibers and focal adhesions, which was dependent on IQGAP1. IQGAP1 was required for hyaluronan- but not for platelet-derived growth factor (PDGF)-BB-induced cell migration, and was required for both hyaluronan- and PDGF-BB-mediated fibroblast proliferation, but not for proliferation induced by 10% fetal bovine serum. Depletion of IQGAP1 suppressed hyaluronan-induced activation of Rac1 and enhanced the activation of RhoA. Taken together, these findings indicate important roles for IQGAP1 in hyaluronan-stimulated migration and proliferation of fibroblasts.
Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 595, SE-75124 Uppsala, Sweden.
Inna
I
Kozlova
Aino
A
Ruusala
Oleksandr
O
Voytyuk
Spyros S
SS
Skandalis
Paraskevi
P
Heldin
D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052816:Foreskin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008297:Male; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D006820:Hyaluronic Acid