Pim proteins (Pim-1, Pim-2 and Pim-3) are oncogene-encoded serine/threonine kinases. Pim-1, a serine/threonine kinase highly expressed in hematopoietic cells, plays a critical role in the transduction of mitogenic signals and is rapidly induced by a variety of growth factors and cytokines. Pim-1 cooperates with c-Myc in lymphoid cell transformation and protects cells from growth factor withdrawal and genotoxic stress-induced apoptosis. Pim-1 also enhances the transcriptional activity of c-Myb through direct phosphorylation within the c-Myb DNA binding domain as well as phosphorylation of the transcriptional coactivator p100. Hypermutations of the Pim-1 gene are found in B-cell diffuse large cell lymphomas. Phosphorylation of Pim-1 at Tyr218 by Etk occurs following IL-6 stimulation and correlates with an increase in Pim-1 activity. Various Pim substrates have been identified; Bad is phosphorylated by both Pim-1 and Pim-2 at Ser112 and this phosphorylation reverses Bad-induced cell apoptosis.The corresponding pim-1 gene encodes a pair of proteins through use of different translation initiation sites. Both larger 44 kDa (Pim-1L) and smaller 33 kDa (Pim-1S) proteins are active kinases, but differ in stability.
