Stimulation by lysosomal enzymes and mannose-6-phosphate of a phosphoprotein phosphatase activity associated with the lysosomal enzyme binding receptor protein from monkey brain.
Previously we have isolated a lysosomal enzyme binding receptor protein from monkey brain that exhibits protein kinase activity and undergoes phosphorylation on serine and tyrosine residues. Using the 32P-labelled receptor protein, we have found that the lysosomal enzyme fucosidase and mannose-6-phosphate, which are ligands for the receptor, stimulated a protein phosphatase activity associated with the receptor protein. Stimulation of protein phosphatase activity using the 32P-labelled receptor protein was demonstrated both by the loss in radioactivity of the receptor and by the release of 32P-phosphate. There was no stimulation by a non-lysosomal glycoprotein enzyme, or by the sugars mannose or glucose. Both serine-phosphate and tyrosine-phosphate residues were dephosphorylated. Stimulation of protein phosphatase activity by fucosidase and mannose-6-phosphate was also demonstrated using as substrate histone 32P-labelled, on serine/threonine or tyrosine residues. Insulin-like growth factor II, another known ligand for the lysosomal enzyme binding receptor, did not show any significant effect, either on the phosphorylation or dephosphorylation of the receptor protein. Our previous and present results suggest that a phosphorylation/dephosphorylation mechanism may be operative in the ligand binding and functions of the receptor.
Department of Neurological Sciences, Christian Medical College Hospital, Vellore, India.
K
K
Panneerselvam
A S
AS
Balasubramanian
D000818:Animals; D001923:Brain Chemistry; D002241:Carbohydrates / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D000882:Haplorhini / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008024:Ligands; D008247:Lysosomes / Q000201:enzymology*; D008360:Mannosephosphates / Q000494:pharmacology*; D009596:Nitrophenols / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D012969:Sodium Fluoride / Q000494:pharmacology; D013268:Stimulation, Chemical; D014638:Vanadates / Q000494:pharmacology; D005644:alpha-L-Fucosidase / Q000494:pharmacology*
D002241:Carbohydrates; D006657:Histones; D008024:Ligands; D008360:Mannosephosphates; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C034304:cation-dependent mannose-6-phosphate receptor; C008644:nitrophenylphosphate; C027693:mannose-6-phosphate; D014638:Vanadates; D007335:Insulin-Like Growth Factor II; D012969:Sodium Fluoride; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; D005644:alpha-L-Fucosidase