PTEN is an important tumor suppressor protein that is commonly mutated in cancer and regulates metastasis and migration. However, the mechanisms by which it does this are currently unclear. P-REX2 is a guanine nucleotide exchange factor that is responsible for controlling migration. Our lab found that P-REX2 binds to PTEN and antagonizes PTEN tumor suppression activity by inhibiting its phosphatase activity. Given that P-REX2 is known to control migration, we set out to determine whether PTEN regulates migration by inhibiting P-REX2. This study attempts to do this by constructing P-REX2 mutants that have been identified to partake in the onset of metastatic melanoma. We used these mutants in GEF and invasion assays and observed that PTEN C2-Tail could inhibit invasion stimulated by WT P-REX2, whereas mutant P-REX2 is resistant to the inhibition by PTEN C2-Tail. We are interested in investigating other potential P-REX2 interactions as well, so behavior between TGF-β RI and P-REX2 will be examined due to a promising high throughput sequencing study. Mutations in TGF-β receptors are known to lead to cancer, so it is possible that these two proteins are related.