Abstract 315: RasGRP1 is a critical link to Ras activation by phorbol esters in mouse epidermal keratinocytes

RasGRP1 is a member of the guanine nucleotide exchange factor family for Ras that binds with high affinity to ultrapotent diacylglycerol analogs like the phorbol esters. Recent work from our lab has demonstrated expression of RasGRP1 in epidermal keratinocytes and a role of this exchange factor in skin carcinogenesis. Further, the studies suggested that RasGRP1 participates in the action of tumor promoting phorbol esters like 12 - tetradecanoylphorbol - O - 13 - acetate (TPA) on Ras pathways in epidermal cells. Given the importance of Ras in epidermal carcinogenesis, we sought to discern if RasGRP1 was a critical pathway in Ras activation, using a RasGRP1 knockout mouse model (KO) to examine the response of primary keratinocytes to TPA. In contrast to the response of wild type (Wt) keratinocytes, which showed a rapid and sustained stimulation of Ras up to 30 minutes in response to TPA (Ras-GTP/Total Ras arbitrary units, 0 min TPA= 0.14 ± 0.06, 30 min TPA= 0.47 ± 0.06; n=5, **p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 315.