Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
1995-1-24
pubmed:abstractText
The heat-stable inhibitor of cAMP-dependent protein kinase (PKI) was shown previously to export the kinase catalytic subunit (C) from the nucleus (Fantozzi, D. A., Harootunian, A. T., Wen, W., Taylor, S. S., Feramisco, J.R., Tsien, R. Y., and Meinkoth, J. L. (1994) J. Biol. Chem. 269, 2676-2686), in addition to its ability to inhibit kinase activity. In this study, the mechanism of PKI export is investigated. The injection of a C-PKI complex containing both labeled PKI and C-subunit revealed that both proteins exit the nucleus in unison. A fusion protein of C-subunit with glutathione S-transferase (GST) (140 kDa) cannot transverse the nuclear membrane in either direction, but can be exported from the nucleus when complexed with PKI, supporting the presence of a nuclear export signal (NES) in the C-PKI complex. Fusions of PKI alpha with GST (70 kDa) or PKI beta 1 with maltose-binding protein (MBP) (50 kDa) remain effective at exporting complexes with C-subunit. The export of C-PKI is also sensitive to temperature and energy depletion. Taken together, these results demonstrate that export is both energy- and temperature-dependent, but size-independent, consistent with an active signal-mediated export process. GST-PKI exits from the nucleus even in the absence of C-subunit, indicating that the NES resides entirely on PKI, but suggesting that fusion of PKI to GST leads to a conformational change that mimics the exposure of the NES caused by the binding of C. Since both PKI alpha and PKI beta 1 can export C-subunit, the predicted export signal is likely to reside on the residues conserved between PKI alpha and PKI beta 1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32214-20
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Heat-stable inhibitors of cAMP-dependent protein kinase carry a nuclear export signal.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093-0654.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't