Inhibition of platelet-derived growth factor-BB-induced receptor activation and fibroblast migration by hyaluronan activation of CD44.
The extracellular matrix molecule hyaluronan was found to suppress platelet-derived growth factor (PDGF) beta-receptor activation and PDGF-BB-induced migration of primary human dermal fibroblasts. The suppressive effect of hyaluronan was neutralized by a monoclonal antibody that specifically inhibits hyaluronan binding to its receptor CD44. Moreover, co-immunoprecipitation experiments showed that the PDGF beta-receptor and CD44 can form a complex. Interestingly, the inhibitory effect of hyaluronan on PDGF beta-receptor activation was not seen in the presence of the tyrosine phosphatase inhibitor pervanadate. Our observations suggest that hyaluronan suppresses PDGF beta-receptor activation by recruiting a CD44-associated tyrosine phosphatase to the receptor.
Li
Lingli
L
Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, Box 595, S-751 24 Uppsala, Sweden.
Heldin
Carl-Henrik
CH
Heldin
Paraskevi
P
D000818:Animals; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism
D018960:Hyaluronan Receptors; D007140:Immunoglobulin Fab Fragments; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D006820:Hyaluronic Acid; D020797:Receptor, Platelet-Derived Growth Factor beta; D017027:Protein Tyrosine Phosphatases