Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2.
Recent evidence suggests that the function of receptors coupled to guanine nucleotide regulatory proteins may be controlled by highly specific protein kinases, e.g. rhodopsin kinase and the beta-adrenergic receptor kinase. In order to investigate the nature of the phosphatases which might be involved in controlling the state of receptor phosphorylation we studied the ability of four highly purified well characterized protein phosphatases to dephosphorylate preparations of rhodopsin or beta 2-adrenergic receptor which had been highly phosphorylated by beta-adrenergic receptor kinase. These included: type 1 phosphatase, calcineurin phosphatase, type 2A phosphatase, and the high molecular weight latent phosphatase 2. Under conditions in which all the phosphatases could dephosphorylate such common substrates as [32P]phosphorylase a and [32P]myelin basic protein at similar rates only the latent phosphatase 2 was active on the phosphorylated receptors. Moreover, a latent phosphatase activity was found predominantly in a sequestered membrane fraction of frog erythrocytes. This parallels the distribution of a beta-adrenergic receptor phosphatase activity recently described in these cells (Sibley, D. R., Strasser, R. H., Benovic, J. L., Daniel, K., and Lefkowitz, R. J. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 9408-9412). These data suggest a potential role for the latent phosphatase 2 as a specific receptor phosphatase.
Yang
S D
SD
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Fong
Y L
YL
Benovic
J L
JL
Sibley
D R
DR
Caron
M G
MG
Lefkowitz
R J
RJ
D000818:Animals; D004910:Erythrocyte Membrane / Q000201:enzymology; D007700:Kinetics; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D054648:Protein Phosphatase 2; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012168:Retinal Pigments / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism*; D013379:Substrate Specificity
D010761:Phosphorus Radioisotopes; D011943:Receptors, Adrenergic, beta; D012168:Retinal Pigments; D012243:Rhodopsin; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2