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Cyclic AMP-dependent proteolysis of GATA-6 expressed on the intracellular membrane
Takeshi Tsuge1, Kae Uetani, Ryuichiro Sato
1Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Abstract:
Cyclic AMP-dependent proteolysis of GATA-6 was characterized by fusing GATA-6 with the carboxyl-terminal membrane domain of SREBP-2. When the fusion protein was stably expressed in CHO-K1 cells, it was recovered in the ER membrane. This protein was processed in a similar manner to SREBP-2 upon cholesterol starvation, and the GATA-6 moiety moved into the nucleus. The GATA-6 moiety on the membrane became undetectable in the presence of dbcAMP or cholera toxin. However, H-89, K-252a, MG115 and lactacystin inhibited this decrease, suggesting that the cytoplasmic GATA-6 moiety of the fusion protein was degraded by proteasomes though A-kinase upon elevation of the cellular cAMP concentration.
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