Studies of hereditary cancer syndromes due to inactivation of tumor suppressor genes have been some of the most informative areas of investigation in the understanding of mechanisms of tumorigenesis. Peutz-Jeghers Syndrome (PJS) is an autosomal dominantly inherited cancer syndrome which predisposes patients to intestinal hamartomatous polyps as well as a wide range of benign and malignant neoplasias. A gene responsible for PJS was recently identified on chromosome 19q13.3 and found to encode a novel serine/threonine kinase. This represents the first example of a kinase acting as a classical tumor suppressor. The goal of this study is to identify key substrates of this novel kinase which may be mediating its tumor suppressor function as well as to characterize the signaling pathways in which this kinase plays a role. Additionally, a conditional targeted disruption of the Peutz-Jeghers' gene will be created to test whether loss of function of this kinase is sufficient to predispose mice to a similar set of tumors, potentially creating a mouse model for PJS. These animals can be used to study tumor development as well as provide cells to study the effects of loss of function of this kinase in the identified signaling pathways.
