title: Studies on protein kinases involved in regulation of nucleocytoplasmic mRNA transport.
abstract: The rate of energy-dependent nucleoside triphosphatase (NTPase)-mediated nucleocytoplasmic translocation of poly(A)-containing mRNA [poly(A)+mRNA] across the nuclear envelope is thought to be regulated by poly(A)-sensitive phosphorylation and dephosphorylation of nuclear-envelope protein. Studying the phosphorylation-related inhibition of the NTPase, we found that phosphorylation of one polypeptide of rat liver envelopes by endogenous NI- and NII-like protein kinase was particularly sensitive to poly(A). This polypeptide (106 kDa) was also phosphorylated by nuclear-envelope-bound Ca2+-activated and phospholipid-dependent protein kinase (protein kinase C). Activation of kinase C by tumour-promoting phorbol esters resulted in inhibition of nuclear-envelope NTPase activity and in a concomitant decrease of mRNA (actin) efflux rate from isolated rat liver nuclei. Protein kinase C, but not nuclear envelope NI-like or NII-like protein kinase, was found to be solubilized from the envelope by Triton X-100, whereas the presumable poly(A)-binding site [the 106 kDa polypeptide, representing the putative carrier for poly(A)+mRNA transport] remained bound to this structure. RNA efflux from detergent-treated nuclei lost its susceptibility to phorbol esters. Addition of purified protein kinase C to these nuclei restored the effect of the tumour promoters. Protein kinase C was found to bind also to isolated rat liver nuclear matrices in the absence but not in the presence of ATP. The NII-like nuclear-envelope protein kinase co-purified together with the 106 kDa polypeptide which specifically binds to poly(A) in an ATP-labile linkage.
authors.affiliation: Institut für Physiologische Chemie, Universität, Mainz, Federal Republic of Germany.
authors.forename: H C
authors.initials: HC
authors.lastname: Schröder
authors.forename: M
authors.initials: M
authors.lastname: Rottmann
authors.forename: R
authors.initials: R
authors.lastname: Wenger
authors.forename: M
authors.initials: M
authors.lastname: Bachmann
authors.forename: A
authors.initials: A
authors.lastname: Dorn
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000201:enzymology / Q000648:ultrastructure; D003593:Cytoplasm / Q000201:enzymology; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000302:isolation & purification; D008854:Microscopy, Electron; D009685:Nuclear Envelope / Q000201:enzymology / Q000648:ultrastructure; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000302:isolation & purification; D010455:Peptides / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D010455:Peptides; D010716:Phosphatidylinositols; D012333:RNA, Messenger; C049312:nuclear pore protein p62; D011061:Poly A; D011493:Protein Kinase C