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Membrane guanylate cyclase is a cell-surface receptor with homology to protein kinases

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Abstract

Guanylate cyclase has been strongly implicated as a cell-surface receptor on spermatozoa for a chemotactic peptide1, and on various other cells as a receptor for atrial natriuretic peptides2–4. Resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH2), the chemotactic peptide released by sea urchin Arbacia punctulata eggs, is specifically crosslinked to A. punctulata spermatozoan guanylate cyclase1. After the binding of the peptide the state of guanylate cyclase phosphorylation modulates enzyme activity1,5,6. We report here that the deduced amino-acid sequence of the spermatozoan membrane form of guanylate cyclase predicts an intrinsic membrane protein of 986 amino acids with an amino-terminal signal sequence. A single transmembrane domain separates the protein into putative extracellular and cytoplasmic-catalytic domains. The cytoplasmic carboxyl-terminal 95 amino acids contain 20% serine, the likely regulatory sites for phosphory-lation. Unexpectedly, the enzyme is homologous to the protein kinase family.

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Authors and Affiliations

  1. The Howard Hughes Medical Institute, Vanderbilt Medical Center, Nashville, Tennessee, 37232, USA

    Sujay Singh, Lawrence J. Dangott, Michael Chinkers & David L. Garbers

  2. Department of Pharmacology, Vanderbilt Medical Center, Nashville, Tennessee, 37232, USA

    Sujay Singh, Michael Chinkers & David L. Garbers

  3. Departments of Molecular Physiology and Biophysics, Vanderbilt Medical Center, Nashville, Tennessee, 37232, USA

    David S. Thorpe, Lawrence J. Dangott & David L. Garbers

  4. Department of Molecular Biology, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    David G. Lowe, Wun-Jing Kuang & David V. Goeddel

  5. Department of Developmental Biology, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    Henry Rodriguez

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  1. Sujay Singh
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  6. Lawrence J. Dangott
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  7. Michael Chinkers
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Singh, S., Lowe, D., Thorpe, D. et al. Membrane guanylate cyclase is a cell-surface receptor with homology to protein kinases. Nature 334, 708–712 (1988). https://doi.org/10.1038/334708a0

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