UC San Diego

Over the last several years, the PHLPP protein phosphatases have emerged as critical regulators of cell signaling. The two PHLPP genes, PHLPP1 and PHLPP2 were originally characterized as hydrophobic motif phosphatases for Akt and PKC. By dephosphorylating these kinases, PHLPP1 and PHLPP2 suppress their proliferative and anti- apoptotic activities. Here, we expand the PHLPP family of enzymes with the cloning of a third member, PHLPP1[Beta]. In addition, we identify the Ras/ERK pathway as a novel target of PHLPP activity, and reveal that PHLPP regulation of this pathway is mediated through control of EGF receptor levels. Finally, we explore the role of PHLPP as a tumor suppressor by sequencing PHLPP1 in CLL patient samples. Together, these studies further our knowledge of the PHLPP family of phosphatases and provide additional evidence in support of a prominent role for PHLPP in controlling growth factor signaling and suppressing tumor growth