Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals

Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals

Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021

Edited by Robert J. Lefkowitz, Duke University Medical Center, Durham, NC, and approved November 6, 1998 (received for review October 13, 1998)

Abstract

Mammals have nine differentially regulated isoforms of G protein-responsive transmembrane-spanning adenylyl cyclases. We now describe the existence of a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or Forskolin regulation. Northern analysis indicates the gene encoding soluble adenylyl cyclase (sAC) is preferentially expressed in testis. As purified from rat testis cytosol, the active form of sAC appears to be a fragment derived from the full-length protein, suggesting a proteolytic mechanism for sAC activation. The two presumptive catalytic domains of sAC are closely related to cyanobacterial adenylyl cyclases, providing an evolutionary link between bacterial and mammalian signaling molecules.

Footnotes

↵ * J.B. and M.L.S. contributed equally to this work.
↵ † To whom reprint requests should be addressed. e-mail: llevin{at}mail.med.cornell.edu.
This paper was submitted directly (Track II) to the Proceedings Office.
Data deposition: The cDNA sequence of rat sAC has been deposited in the GenBank database (accession no. AF081941).
ABBREVIATIONS:

AC,

adenylyl cyclase;

tmACs,

transmembrane adenylyl cyclases;

sAC,

soluble form of AC;

RT-PCR,

reverse transcription–PCR