The cGMP sensitivity of cyclic nucleotide–gated (CNG) channels can be modulated by changes in phosphorylation catalyzed by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases. Previously, we used genistein, a PTK inhibitor, to probe the interaction between PTKs and homomeric channels comprised of α subunits (RETα) of rod photoreceptor CNG channels expressed in Xenopus oocytes. We showed that in addition to inhibiting phosphorylation, genistein triggers a noncatalytic interaction between PTKs and homomeric RETα channels that allosterically inhibits channel gating. Here, we show that native CNG channels from rods, cones, and olfactory receptor neurons also exhibit noncatalytic inhibition induced by genistein, suggesting that in each of these sensory cells, CNG channels are part of a regulatory complex that contains PTKs. Native CNG channels are heteromers, containing β as well as α subunits. To determine the contributions of α and β subunits to genistein inhibition, we compared the effect of genistein on native, homomeric (RETα and OLFα), and heteromeric (RETα+β, OLFα+β, and OLFα+RETβ) CNG channels. We found that genistein only inhibits channels that contain either the RETα or the OLFβ subunits. This finding, along with other observations about the maximal effect of genistein and the Hill coefficient of genistein inhibition, suggests that the RETα and OLFβ subunits contain binding sites for the PTK, whereas RETβ and OLFα subunits do not.
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1 June 2000
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June 01 2000
Interactions of Cyclic Nucleotide-Gated Channel Subunits and Protein Tyrosine Kinase Probed with Genistein
Elena Molokanova,
Elena Molokanova
aDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33101
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Alexei Savchenko,
Alexei Savchenko
aDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33101
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Richard H. Kramer
Richard H. Kramer
aDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33101
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Elena Molokanova
aDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33101
Alexei Savchenko
aDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33101
Richard H. Kramer
aDepartment of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33101
Dr. Savchenko's present address is Affymax Research Institute, Palo Alto, CA 94304.
Abbreviations used in this paper: AMP-PNP, adenylylimidodiphosphate; CNG, cyclic nucleotide-gated; PTK, protein tyrosine kinase; PTP, protein tyrosine phosphatase.
Received:
December 31 1999
Revision Requested:
March 31 2000
Accepted:
April 11 2000
Online ISSN: 1540-7748
Print ISSN: 0022-1295
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Gen Physiol (2000) 115 (6): 685–696.
Article history
Received:
December 31 1999
Revision Requested:
March 31 2000
Accepted:
April 11 2000
Citation
Elena Molokanova, Alexei Savchenko, Richard H. Kramer; Interactions of Cyclic Nucleotide-Gated Channel Subunits and Protein Tyrosine Kinase Probed with Genistein. J Gen Physiol 1 June 2000; 115 (6): 685–696. doi: https://doi.org/10.1085/jgp.115.6.685
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