title: [The Pim family of protein kinases: structure, functions and roles in hematopoietic malignancies].
abstract: Phosphorylation is the universal regulatory mechanism in key physiological processes such as development, cell differentiation, proliferation, survival and malignant transformation. In this review we analyze serine/threonine protein kinases of the Pim (proviral integration of Moloney virus) family that have been initially discovered in experimental lymphomas. We provide data on gene structure, evolution, functions and substrates of Pim protein kinases. Focusing on Pim-1 as the major isoform, we analyze its role in the biology of hematopoietic malignancies. Pim-1 is a pro-proliferative and pro-survival protein kinase. It is constitutively active due to autophosphorylation, and its downstream partners positively regulate the cell cycle. Pim-1 cooperates with c-Myc oncoprotein in leukemogenesis; furthermore, Pim-1, like the Akt protein kinase, prevents cell death. Thus, Pim kinases are regarded as new therapeutic targets. Finally, we present an original test system f or screening of Pim inhibitors. In this test system the growth of a genetically engineered Escherichia coli strain in the presence of kanamycin is dependent on the phosphorylation of aminoglycoside-3' phosphotransferase VIII by Pim-1: pharmacological inhibition of this phosphorylation increases the bacterial cell lysis.
authors.forename: Iu N
authors.initials: IuN
authors.lastname: Zhukova
authors.forename: M G
authors.initials: MG
authors.lastname: Alekseeva
authors.forename: N V
authors.initials: NV
authors.lastname: Zakharevich
authors.forename: A A
authors.initials: AA
authors.lastname: Shtil'
authors.forename: V N
authors.initials: VN
authors.lastname: Danilenko
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D057166:High-Throughput Screening Assays; D006801:Humans; D007612:Kanamycin; D019868:Kanamycin Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008958:Models, Molecular; D010766:Phosphorylation; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D007612:Kanamycin; D019868:Kanamycin Kinase; D051057:Proto-Oncogene Proteins c-akt; D051573:Proto-Oncogene Proteins c-pim-1