Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Graded doses of ochratoxin A incorporated into the diet (0, 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/g) of broiler chickens significantly (P < 0.05) inhibited activity of protein kinase, the initiator enzyme of the glycogen phosphorylase system, in the livers at all dose levels. Only the highest dose, 8.0 micrograms/g, significantly reduced the total activity of phosphorylase kinase, which is activated by protein kinase. The total activity of phosphorylase, which is activated by phosphorylase kinase, was unaltered by ochratoxin A at any level. Additon of ochratoxin A to liver extracts control birds inhibited protein kinase but not phosphorylase kinase. When added to extracts of livers from control birds, cyclic adenosine 3',5'-monophosphate stimulated protein kinase but not phosphorylase kinase. The cyclic adenosine 3',5'-monophosphate had no effect when added to extracts from birds fed ochratoxin A. These results suggest that ochratoxin A affects primarily the cyclic adenosine 3',5'-monophosphate-dependent protein kinase which initiates the enzymatic cascade leading to glycogenolysis. Furthermore, these results conform an earlier assignment on morphological criteria of the glycogenosis of ochratoxicosis as a type X glycogen storage disease.
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PMID:Inhibition of the glycogen phosphorylase system during ochratoxicosis in chickens. 625 38

A five-month-old Japanese boy was found to have marked glycogen accumulation only in the heart. A survey of enzymes revealed normal activities of phosphorylase, cyclic AMP-dependent protein kinase, acid maltase and amylo-1,6-glucosidase. However, the heart had capacity of activating neither rabbit muscle phosphorylase b nor endogenous phosphorylase b, which was converted to active form only when supplemented rabbit muscle phosphorylase kinase. In contrast to the heart, activities of phosphorylase kinase were found within normal levels in other organ tissues so far tested. These findings indicate that the present case of the cardiac glycogenosis is caused by deficiency of cardiac phosphorylase kinase.
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PMID:A new type of glycogen storage disease caused by deficiency of cardiac phosphorylase kinase. 642 67

Muscle-specific deficiency of phosphorylase kinase (Phk) causes glycogen storage disease, clinically manifesting in exercise intolerance with early fatiguability, pain, cramps and occasionally myoglobinuria. In two patients and in a mouse mutant with muscle Phk deficiency, mutations were previously found in the muscle isoform of the Phk alpha subunit, encoded by the X-chromosomal PHKA1 gene (MIM # 311870). No mutations have been identified in the muscle isoform of the Phk gamma subunit (PHKG1). In the present study, we determined Q1the structure of the PHKG1 gene and characterized its relationship to several pseudogenes. In six patients with adult- or juvenile-onset muscle glycogenosis and low Phk activity, we then searched for mutations in eight candidate genes. The coding sequences of all six genes that contribute to Phk in muscle were analysed: PHKA1, PHKB, PHKG1, CALM1, CALM2 and CALM3. We also analysed the genes of the muscle isoform of glycogen phosphorylase (PYGM), of a muscle-specific regulatory subunit of the AMP-dependent protein kinase (PRKAG3), and the promoter regions of PHKA1, PHKB and PHKG1. Only in one male patient did we find a PHKA1 missense mutation (D299V) that explains the enzyme deficiency. Two patients were heterozygous for single amino-acid replacements in PHKB that are of unclear significance (Q657K and Y770C). No sequence abnormalities were found in the other three patients. If these results can be generalized, only a fraction of cases with muscle glycogenosis and a biochemical diagnosis of low Phk activity are caused by coding, splice-site or promoter mutations in PHKA1, PHKG1 or other Phk subunit genes. Most patients with this diagnosis probably are affected either by elusive mutations of Phk subunit genes or by defects in other, unidentified genes.
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PMID:Muscle glycogenosis with low phosphorylase kinase activity: mutations in PHKA1, PHKG1 or six other candidate genes explain only a minority of cases. 1282 73

Glycogen storage disease (GSD) type IX is a rare disease of variable clinical severity affecting primarily the liver tissue. Individuals with liver phosphorylase b kinase (PhK) deficiency (GSD IX) can present with hepatomegaly with elevated serum transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth with considerable variation in clinical severity. PhK is a cAMP-dependent protein kinase that phosphorylates the inactive form of glycogen phosphorylase, phosphorylase b, to produce the active form, phosphorylase a. PhK is a heterotetramer; the alpha 2 subunit in the liver is encoded by the X-linked PHKA2 gene. About 75% of individuals with liver PhK deficiency have mutations in the PHKA2 gene; this condition is also known as X-linked glycogenosis (XLG). Here we report the variability in clinical severity and laboratory findings in 12 male patients from 10 different families with X-linked liver PhK deficiency caused by mutations in PHKA2. We found that there is variability in the severity of clinical features, including hypoglycemia and growth. We also report additional PHKA2 variants that were identified in 24 patients suspected to have liver PhK deficiency. The basis of the clinical variation in GSDIX due to X-linked PHKA2 gene mutations is currently not well understood. Creating systematic registries, and collecting longitudinal data may help in better understanding of this rare, but common, glycogen storage disorder.
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PMID:Clinical and Molecular Variability in Patients with PHKA2 Variants and Liver Phosphorylase b Kinase Deficiency. 2828 41