Melanoma is a highly aggressive tumor associated with environmental exposure to UV radiation. Melanomas are refractory to treatment if not detected early, and identification of new therapeutic targets is urgently needed. Human melanomas frequently exhibit deregulation of protein kinase signaling pathways, including activating mutations in BRAF, upregulation of Akt activity, and loss of the CDKN2A locus, which deregulates the downstream pRb pathway cyclin-dependent kinases cdk4 and cdk6. A mouse model of melanoma has recently been developed in which oncogenic BRAF (BRAFV600E) targeted specifically to melanocytes drives formation of nevus-like hyperplasias and melanomas, which show activation of Akt and CDKN2A loss. Preliminary studies have shown preferential upregulation and activation of the Akt3 isoform during melanomagenesis in BRAFV600E transgenic mice. My research will focus on determining the requirement for Akt3 and downstream kinases in the development and progression of BRAF-driven melanoma, as well as in UV-induced melanoma. The kinases targeted in our studies are largely dispensable for normal cellular development and function; if they are required for the development of melanoma or for sustained melanoma cell proliferation, pharmacological inhibition of these kinases may represent a new therapeutic approach to selectively target tumor cells while minimizing side effects in non-tumor tissues.