Dopamine- and cAMP-Regulated Phosphoprotein DARPP-32: Phosphorylation of Ser-137 by Casein Kinase I Inhibits Dephosphorylation of Thr-34 by Calcineurin

Although protein phosphatases appear to be highly controlled in intact cells, relatively little is known about the physiological regulation of their activity. DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of apparent Mr32,000, is phosphorylated in vitro by casein kinase I, casein kinase II...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-03, Vol.92 (7), p.2682-2685
Main Authors: Desdouits, Frederic, Siciliano, Julio C., Greengard, Paul, Girault, Jean-Antoine
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies
Calcineurin
Calcium - pharmacology
Calmodulin - pharmacology
Calmodulin-Binding Proteins - antagonists & inhibitors
Calmodulin-Binding Proteins - metabolism
Casein Kinases
Cattle
Cellular biology
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Dopamine - metabolism
Dopamine and cAMP-Regulated Phosphoprotein 32
Immunoblotting
Kinetics
Manganese - pharmacology
Muscle, Skeletal - enzymology
Myocardium - enzymology
Nerve Tissue Proteins - metabolism
Neurology
Neurons
Neuroscience
Phosphatases
Phosphoprotein Phosphatases - antagonists & inhibitors
Phosphoprotein Phosphatases - metabolism
Phosphoproteins
Phosphoproteins - metabolism
Phosphorylation
Phosphoserine - analysis
Phosphothreonine - analysis
Physiological regulation
Protein Kinases - metabolism
Protein Phosphatase 1
Proteins
Rabbits
Rats
Receptors
Recombinant Proteins - metabolism
Serine
Stoichiometry
Substantia Nigra - metabolism
Threonine
Thymus Gland - enzymology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although protein phosphatases appear to be highly controlled in intact cells, relatively little is known about the physiological regulation of their activity. DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of apparent Mr32,000, is phosphorylated in vitro by casein kinase I, casein kinase II, and cAMP-dependent protein kinase on sites phosphorylated in vivo. DARPP-32 phosphorylated on Thr-34 by cAMP-dependent protein kinase is a potent inhibitor of protein phosphatase 1 and an excellent substrate for calcineurin, a Ca2+/calmodulin-dependent protein phosphatase. Here we provide evidence, using both purified proteins and brain slices, that phosphorylation of DARPP-32 on Ser-137 by casein kinase I inhibits the dephosphorylation of Thr-34 by calcineurin. This inhibition occurs only when phospho-Ser-137 and phospho-Thr-34 are located on the same DARPP-32 molecule and is not dependent on the mode of activation of calcineurin. The results demonstrate that the inhibition is due to a modification in the properties of the substrate which alters its dephosphorylation rate. Thus, casein kinase I may play a physiological role in striatonigral neurons as a modulator of the regulation of protein phosphatase 1 via DARPP-32.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.7.2682