Signal transduction through the cAMP-dependent protein kinase.
Temporal cellular events responsible for hormonal activation of responses mediated by the cAMP-dependent protein kinase (PKA) have been studied in living cells. By selectively perturbing molecular function of Gs, the catalytic subunit of PKA (C), or the nuclear factor CREB, in cells through microinjection of inhibitory agents specific for these molecules or activated forms of these molecules, we have obtained evidence for a requirement for the function of each of these molecules in the hormonal stimulation of cAMP-regulated genes. Moreover, by introducing fluorescently labeled PKA subunits into these cells as molecular tracers, or by immunofluorescence of C subunit, we have observed biological translocation of C subunit from the cytoplasm to the nucleus during transcriptional activation and a quenching of this by the inhibitor molecule, PKI. The implications of these cellular and molecular events in the signal transduction of hormonal responses are discussed.
Meinkoth
J L
JL
Department of Medicine, University of California at San Diego, La Jolla 92093-0636.
Alberts
A S
AS
Went
W
W
Fantozzi
D
D
Taylor
S S
SS
Hagiwara
M
M
Montminy
M
M
Feramisco
J R
JR
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D046911:Macromolecular Substances; D015398:Signal Transduction; D013972:Thyrotropin / Q000494:pharmacology
D017362:Cyclic AMP Response Element-Binding Protein; D046911:Macromolecular Substances; D013972:Thyrotropin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins