The invention relates to novel polynucleotides and their encoded gene products that are expressed in skin cells, particularly keratinocytes, and methods of using the same. Specifically, the present invention provides polynucleotides encoding several novel protein kinases that are c-Jun N-terminal kinase kinase kinases, i.e., MLK4, PAK4, PAK5 and YSK2. In addition, the invention provides methods of using the disclosed polynucleotides and their gene products in drug discovery, particularly in screening for drugs that can reduce ultraviolet light-induced damage of the skin, inflammation and psoriasis, and drugs that can enhance wound healing.