Abstract
Previous results from our laboratory have shown that phosphorylation of type VI adenylyl cyclase (ACVI) by protein kinase C (PKC) caused suppression of adenylyl cyclase activity. In the present study, we investigated the role of the N terminus cytosolic domain of ACVI in this PKC-mediated inhibition of ACVI. Removal of amino acids 1 to 86 of ACVI or mutation of Ser10 (a potential PKC phosphorylation site) into alanine significantly relieved the PKC-mediated inhibition and markedly reduced the PKC-evoked protein phosphorylation. PKC also effectively phosphorylated a recombinant N terminus cytosolic domain (amino acids 1–160) protein of ACVI and a synthetic peptide representing Ser10. In addition, the amino acids 1 to 86 truncated mutant exhibited kinetic properties similar to those of the wild type. Taken together, these data demonstrate that the highly variable N terminus cytoplasmic domain of ACVI is a regulatory domain with a critical role in PKC-mediated suppression, which is a hallmark of this adenylyl cyclase isozyme. In addition, Ser10 was found to serve as an acceptor for the PKC-mediated phosphorylating transfer of ACVI.
Footnotes
- Received March 1, 1999.
- Accepted June 11, 1999.
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Send reprint requests to: Dr. Yijuang Chern, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, Republic of China. E-mail: BMYCHERN{at}ibms.sinica.edu.tw
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↵1 H.-L. L. and T.-H. L. contributed equally to this work.
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↵2 Present address: Department of Life Sciences, Chung Shan Medical and Dental College, Taichung 402, Taiwan, Republic of China.
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This work was supported by grants from National Science Council (NSC87–2314-B001–013) and from Academia Sinica, Taipei, Taiwan, Republic of China.
- The American Society for Pharmacology and Experimental Therapeutics
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