Hyaluronan (HA) triggers a wide variety of cellular functions, yet its sign
aling pathway remains largely unclear. We found that HA-treatment of 3Y1 ce
lls activated tyrosine phosphorylation of cellular proteins and mitogen-act
ivated protein (MAP) kinase in a time- and dose-dependent manner, and, subs
equently, stimulated cell growth. This HA-activity was resistant to boiling
at 100 degrees C but completely abolished by treatment with hyaluronidase,
suggesting that HA itself, but not any HA-associated proteins, has the act
ivity. In addition, we found that HA-dependent activation of MAP kinase was
strongly suppressed by the expression of dominant negative ras (S17N ras).
These results suggest that Pas-MAP kinase pathway is activated by HA and m
ay play an important role in HA-dependent signaling.