title: Nuclear import of protein kinases and cyclins.
abstract: Karyophilic and acidic clusters were found in most nonmembrane serine/threonine protein kinases whose primary structure was examined. These karyophilic clusters might mediate the anchoring of the kinase molecules to transporter proteins for their regulated nuclear import and might constitute the nuclear localization signals (NLS) of the kinase molecules. In contrast to protein transcription factors that are exclusively nuclear possessing strong karyophilic peptides composed of at least four arginines (R) and lysines (K) within an hexapeptide flanked by proline and glycine helix-breakers, protein kinases often contain one histidine and three K+R residues; this is proposed to specify a weak NLS structure resulting in the nuclear import of a fraction of the total cytoplasmic kinase molecules as well as in their weak retention in the different ionic strength nuclear environment. Putative NLS peptides in protein kinases may also contain hydrophobic or bulky aromatic amino acids proposed to further diminish their capacity to act as strong NLS. Most kinases lacking karyophilic clusters (c-Mos, v-Mos, sea star MAP, and yeast KIN28, SRA1, SRA3, TPK1, TPK2) also lack acidic clusters, which is in contrast to most kinases containing both acidic and karyophilic peptides; this and the presence of R/K clusters in the transporter proteins supports a role of acidic clusters on kinases in nuclear import. Cyclins B lack karyophilic signals and are proposed to be imported into nuclei via their association with Cdc2.
authors.affiliation: Institute of Molecular Medical Sciences, Palo Alto, California 94306, USA.
authors.forename: T
authors.initials: T
authors.lastname: Boulikas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002453:Cell Cycle; D002467:Cell Nucleus / Q000201:enzymology*; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D016213:Cyclins; D011494:Protein Kinases