Activation of cell surface components has been implicated in the activation of downstream signaling cascade in response to UV irradiation, and yet the identity and the interaction of those components have been scantly documented. Accumulating evidence indicates that caveolae encapsulating
caveolins is the location for those interactions. We found in cultured human keratinocytes that UV irradiation induced both
caveolin-1 and EGFR phosphorylation.
Filipin, a caveolae disruptive agent, inhibited UV-induced
caveolin-1 activation. Na+-K+-
ATPase catalyzes active transport of Na+ and K+ across plasma membrane of mammalian cells, inactivation of which has recently been shown to be involved in the activation of signal transduction pathways including MAP kinase cascade. We found in this study that UV inactivated Na+-K+-
ATPase in time-dependent manner, Na+-K+-
ATPase activity started to decrease 5 min post UV irradiation and reduced to 60% of its original activity within 1 h. Pretreatment with Flipin and
MMP inhibitor recovered Na+-K+-
ATPase activity lost by UV irradiation. ECIS analysis indicated that both
EGF treatment and UV irradiation increased membrane electric activity which was inhibited by
MMP inhibitor and
Filipin. Further study showed that pretreatment of human keratinocytes with
MMP inhibitor or
Filipin inhibited UV-induced phosphorylation of p38 and JNK, which was however not observed in LnCap cells, a
prostate cancer cell line lacking
caveolin-1. UV irradiation also induced ectodomain shedding of
HB-EGF in a time-dependent manner in keratinocytes. Collectively, we conclude that UV-induced MAP
kinase activation is mediated by
cell surface receptor activation due to the matrix activity and membrane caveolae function and inactivation of Na+-K+-
ATPase.