CUP Faculty Research
Cell Death-Induced Activation of Epidermal Growth Factor Receptor in Keratinocytes: Implications for Restricting Epidermal Damage in Dermatitis
Recent findings have implicated Fas/Fas ligand (FasL) in mediating the death of keratinocytes in spongiotic lesions. We asked whether dying keratinocytes could potentially initiate a protective response of the skin to limit the destruction of the epidermis in the spongiotic areas. In addition to apoptosis, treatment of keratinocyte cultures in vitro with FasL triggers a profound phoshorylation of the epidermal growth factor receptor (EGFR) and of its downstream effectors ERK and protein kinase B (PKB/Akt). Using a variety of inhibitors and blocking antibodies, we demonstrated that: (i) apoptosis is required for the generation of the signal(s) leading to the activation of EGFR, ERK, and Akt; (ii) the activation of EGFR, ERK, and Akt by FasL is indeed mediated by its bona fide receptor Fas; (iii) the activation of EGFR is essential for the subsequent activation of ERK and Akt; and (iv) apoptotic keratinocytes secrete soluble EGFR ligands (including amphiregulin) that are processed from membrane-bound proligand forms by metalloproteinase(s). Our findings demonstrate a potential mechanism for the restriction and repair of spongiotic damage in eczemas.
Journal of Investigative Dermatology
Iordanov, Mihail S.; Sundholm, Aaron J.; Simpson, Eric L.; Hanifin, Jon M.; Ryabinina, Olga P.; Choi, Remy J.; Korcheva, Veselina B.; Schneider, Pascal; and Magun, Bruce E., "Cell Death-Induced Activation of Epidermal Growth Factor Receptor in Keratinocytes: Implications for Restricting Epidermal Damage in Dermatitis" (2005). CUP Faculty Research. 112.
CU Commons -- Math and Science Department Faculty Research
Iordanov, M. S., Sundholm, A. J., Simpson, E. L., Hanifin, J. M., Ryabinina, O. P., Choi, R. J., Korcheva, V. B., Schneider, P., & Magun, B. E. (2005). Cell death-induced activation of epidermal growth factor receptor in keratinocytes: Implications for restricting epidermal damage in dermatitis. Journal of Investigative Dermatology, 125(1), 134-142. doi:10.1111/j.0022-202X.2005.23804.x