prostaglandin-d2 and staurosporine-aglycone

Cyclic AMP-dependent proteolysis of GATA-6(Delta50) was characterized using inhibitors for intracellular signaling pathways. Among these kinase inhibitors, only H-89 and K252a inhibited the proteolysis induced by dbcAMP, a membrane permeable cAMP analogue, others such as PD98059, SB203580, calphostine C, PP1, and KN-93 did not do so. These results suggest that A-kinase, but not C-kinase, MEK, P38 MAP-kinases or Src kinase, could participate in the observed phenomenon. We further demonstrated that an inhibitor for ubiquitin isopeptidase (Delta12-PGJ2) inhibited the degradation of GATA-6(Delta50) in the presence of dbcAMP, suggesting that the cAMP-dependent proteolysis could be mediated through the ubiquitin-proteasome pathway, although proteasome activity did not change significantly during dbcAMP treatment. The full-length GATA-6 was also responsive to the induced degradation. Furthermore, mutation of a potential phosphorylation site (Ser-290-->Ala) for A- and C-kinases, and deletion of the PEST sequence of GATA-6 did not abolish the degradation. All these results suggest that cellular factor(s) may play a crucial role in mediating the activation of the cAMP-dependent process.

Topics: Animals; Base Sequence; Benzylamines; Binding Sites; Bucladesine; Carbazoles; Cell Nucleus; CHO Cells; Cricetinae; Cyclic AMP; DNA-Binding Proteins; Enzyme Inhibitors; Flavonoids; GATA6 Transcription Factor; Humans; Imidazoles; Indole Alkaloids; Isoquinolines; MAP Kinase Kinase Kinase 1; MAP Kinase Signaling System; Molecular Sequence Data; Mutation; Naphthalenes; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Plasmids; Prostaglandin D2; Proteasome Endopeptidase Complex; Protein Binding; Pyridines; src-Family Kinases; Sulfonamides; Transcription Factors