Mechanisms of regulation and functions of guanylyl cyclases

  • D. C. Foster
  • B. J. Wedel
  • S. W. Robinson
  • D. L. Garbers
Chapter

Abstract

Although enormous progress in understanding guanylyl cyclase structure and regulation has been recently made, many questions remain. There are now numerous guanylyl cyclase sequences, and signature sequences for discrete domains within these molecules can be identified. The majority of the guanylyl cyclases identified, however are orphan receptors. A primary goal, therefore, is the identification of ligands for the numerous orphan receptor guanylyl cyclases. Identification of these molecules may provide insight into systems such as vision and olfaction among others. In addition, it will be of interest to identify guanylyl cyclase regulatory proteins. These molecules may provide insight into guanylyl cyclase regulation and provide targets for other signaling pathways to modulate guanylyl cyclase activity. Finally, the information gained from structural studies of adenylyl cyclase has shed new light on the guanylyl cyclase catalytic domain, and raised the possibility of a previously unidentified regulatory pocket within the catalytic domain. Understanding the role of this potential regulatory region may provide new insight into not only guanylyl cyclase regulation, but numerous physiological processes.

Abbreviations

NO

nitric oxide

CO

carbon monoxide

ANP

atrial natriuretic peptide

AMPPNP

5′-adenylylimidodiphosphate

ATPγS

adenosine 5′-O-thiotriphosphate

2′d3′ AMP

2′-deoxyadenosine 3′-monophosphate

sGC

soluble guanylyl cyclase

mGC

membrane guanylyl cyclase

AC

adenylyl cyclase

STa

heat-stable enterotoxin of E. coli

PKC

protein kinase C

GC-A-G

guanylyl cyclase A-G

TM

transmembrane domain

ECD

extracellular domain

KHD

kinase homology domain

DD

dimerization domain

CHD

cyclase homology domain

HBD

heme binding domain

ODQ

1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • D. C. Foster
    • 1
  • B. J. Wedel
    • 1
  • S. W. Robinson
    • 1
  • D. L. Garbers
    • 1
  1. 1.Howard Hughes Medical Institute and Department of PharmacologyUniversity of Texas Southwestern Medical CenterDallas

Personalised recommendations