Dephosphorylation of the guanylyl cyclase-A receptor causes desensitization
Atrial natriuretic peptide (ANP) binds to the guanylyl cyclase-A (GC-A) receptor found in tissues such as the kidney and adrenal gland, resulting in marked elevations of the intracellular signaling molecule, cGMP. Here, GC-A is shown to exist as a phosphoprotein when expressed in human embryonic 293...
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Veröffentlicht in: | The Journal of biological chemistry 1992-07, Vol.267 (21), p.14531-14534 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Atrial natriuretic peptide (ANP) binds to the guanylyl cyclase-A (GC-A) receptor found in tissues such as the kidney and adrenal
gland, resulting in marked elevations of the intracellular signaling molecule, cGMP. Here, GC-A is shown to exist as a phosphoprotein
when expressed in human embryonic 293 cells. The 32P is principally associated with phosphoserine, with only trace amounts
of phosphothreonine. The addition of ANP causes a time-dependent dephosphorylation of the receptor, as well as desensitization,
which is not due to an ANP-mediated decrease in the amount of receptor protein. The mobility of GC-A on sodium dodecyl sulfate-polyacrylamide
gel electrophoresis increases after treatment of cells with ANP, and protein phosphatase 2A induces the same mobility shift.
The protein phosphatase also catalyzes dephosphorylation of GC-A, and this is directly correlated with decreases in ANP-stimulatable
guanylyl cyclase activity. Okadaic acid, an inhibitor of protein phosphatase 2A, blocks both the dephosphorylation and the
desensitization. Therefore, in contrast to many other cell surface receptors, GC-A is desensitized by ligand-induced dephosphorylation. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/s0021-9258(18)42069-8 |