PIM

The PIM group encodes three highly related serine/threonine kinases, PIM1, PIM2, and PIM3, originally identified as proviral integration sites in Moloney murine leukemia virus-induced lymphomas. Unlike most kinases they are constitutively active without a regulatory domain or activation-loop phosphorylation requirement. Their expression is driven by cytokines through JAK/STAT signaling, particularly STAT5. They promote cell survival, proliferation, and metabolism by phosphorylating BAD, eIF4B, c-MYC, and PRAS40, cooperating with MYC in lymphoma. Overexpression occurs in leukemias, lymphomas, prostate cancer, and multiple myeloma. Pan-PIM inhibitors are in clinical development, and PIM kinases help tumors evade targeted therapies, marking them as combination therapy partners.