Receptors and Signal Transduction Pathways Involved in Autonomic Responses
Kenneth J. Broadley in Autonomic Pharmacology, 2017
cAMP serves as a second messenger in many varied physiological events by activating cAMP-dependent protein kinase (PKA). This enzyme exists as a tetramer (R2C2) consisting of two regulatory subunits (R) and two catalytic subunits (C). Two molecules of cAMP bind to each regulatory subunit causing the dissociation of two activated catalytic subunits. These catalyse the phosphorylation of a wide range of proteins, and in glycogenolysis phosphorylase kinase is activated. This enzyme is also partially activated by a rise in intracellular Ca2+ which will accompany increases in cardiac muscle contractility induced by β-adrenoceptor stimulation and hence assist in energy provision. Activated phosphorylase kinase converts phosphorylase b (inactive) to phosphorylase a (active) by phosphorylation of a serine residue (Ser-14). This is the enzyme that controls the rate-limiting step in glycogenolysis, whereby glucose units are removed sequentially, as glucose-1-phosphate, from the glycogen polymer by phosphorolytic cleavage of the α-1,4 linkages. By the action of phosphoglucomutase, this in turn is converted to glucose-6-phosphate, which is utilized as a major energy source in muscles by incorporation into glycolysis pathways with the ultimate generation of ATP and pyruvate.
Signalling Pathways in The Regulation of Cellular Responses to Exercise
Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse in The Routledge Handbook on Biochemistry of Exercise, 2020
Adrenalin signalling is initiated when adrenaline binds to the G-coupled β2-adrenergic receptor in SkM leading to increased activity of adenylate cyclase with generation of cyclic AMP (cAMP). This is followed by activation of protein kinase A (PKA) through cAMP-induced dissociation of the catalytic and regulatory PKA subunits. The activated catalytic PKA phosphorylates glycogen phosphorylase kinase, which by phosphorylation converts glycogen phosphorylase from the inactive to the active form. Moreover, PKA has been reported to inactivate glycogen synthase by direct phosphorylation of site 2, 1a and 1b (87). In addition, PKA translocates to the nucleus with concomitant phosphorylation of target proteins, including CREB. Phosphorylated and activated CREB binds to the cAMP response element in the promoter region of target genes, which has been suggested to include PGC-1α, resulting in enhanced transcriptional activity (Figure 8.2).
Reactivities of Amino Acids and Proteins with Iodine
Erwin Regoeczi in Iodine-Labeled Plasma Proteins, 2019
Tyrosine-O-phosphate is encountered at subcellular level, its biological significance being currently in the focus of interest. Protein phosphorylation has, of course, been much studied in the past, for many neurotransmitters, hormones, and other substances that can be regarded as regulatory agents affect the phosphorylation of specific proteins in their target tissues.275 Cell metabolism, transport across membranes, actomyosin function, and expression of genetic information are a few examples of biological events where protein phosphorylation plays a major role. A protein kinase (i.e., an enzyme catalyzing the transfer of phosphate on to a protein) may depend on cyclic AMP, in which case cyclic AMP activates the protein kinase directly by dissociating inhibitory substances from the catalytic subunit of the enzyme. Such a cyclic AMP-dependent protein kinase regulates, for example, the activity of phosphorylase kinase, glycogen synthetase, and lipase. Many regulatory agents, however, stimulate protein phosphorylation independently of cyclic AMP.
The Diagnostic Yield of Electromyography at Detecting Abnormalities on Muscle Biopsy: A Single Center Experience
Published in The Neurodiagnostic Journal, 2021
Patrick B. Moloney, Stela Lefter, Aisling M. Ryan, Michael Jansen, Niamh Bermingham, Brian McNamara
Binary diagnostic outcomes (normal or abnormal) for EMG and muscle biopsy are shown in Figure 1. Abnormal EMG produced sensitivity of 87% and a PPV of 89% for abnormal muscle biopsy. Seventeen “false negative” (normal EMG and abnormal muscle biopsy) cases were identified, of which 13 had myopathic findings and 4 had neurogenic findings on muscle biopsy. Six of those “false negative” cases had pathological features consistent with a specific myopathy: mitochondrial myopathy in 4 cases; central core myopathy in 1 case; and a glycogen metabolism disorder in 1 case (phosphorylase kinase deficiency confirmed by genetic testing). There were 14 “false positive” (abnormal EMG and normal muscle biopsy) studies, of which 8 had myopathic findings and 6 had neurogenic findings on EMG.
The role of CaMK4 in immune responses
Published in Modern Rheumatology, 2018
Tomohiro Koga, Atsushi Kawakami
Calcium/calmodulin-dependent protein kinases (CaMKs) are enzymes activated similarly by calcium flux. Members of the CaMK family are classified into two classes based on their function. There are multifunctional CaMKs (CaMKK, CaMK1, CaMK2 and CaMK4) which each have several substrates and substrate-specific CaMKs (CaMK3, phosphorylase kinase, and the myosin light chain kinases) that have a single substrate [9]. Among the CaMK family, CaMK2 and CaMK4 have shown to play important roles in immune responses including T-cell activation [10,11] and T-cell development [12,13]. Comparing that CaMK2 induces NF-κB related signals [14], CaMK4 activates various transcription factors [15].
Dietary Turmeric Bisdemethoxycurcumin Suppresses Wilms’ Tumor 1 and CD34 Protein Expressions in KG-1a Leukemic Stem Cells
Published in Nutrition and Cancer, 2019
Pawaret Panyajai, Singkome Tima, Sawitree Chiampanichayakul, Songyot Anuchapreeda
Since the LSC population in the KG-1a cells made up more than 90% of the cell population, the cells should not be isolated by magnetic cell sorting and were used for studying the effects of in-house turmeric curcuminoids on WT1 protein expression in LSCs. Based on the study of WT1 protein expressions in leukemic cell lines, noncytotoxic doses (IC20 values) of all curcuminoids including CS, standard C1, standard C2, standard C3, CM, in-house C1, in-house C2, and in-house C3 were examined. It was observed that after the curcuminoid treatments, all the curcuminoids could decrease the WT1 protein expressions in the KG-1a cells. Unlike many previous experiments, results in several studies have shown that pure curcumin (C1) is the most effective compound among curcuminoids, as far as the inhibition of WT1 protein expressions is concerned, when it comes to leukemic cell lines (24), as well as cancer cell proliferation (31). This study demonstrated that noncytotoxic doses of bisdemethoxycurcumin (C3) exhibit considerably strong inhibitory effects on the WT1 protein expressions in KG-1a LSCs. In contrast, the curcuminoid mixture and pure curcumin showed lower inhibitory effects on KG-1a cells. However, the treatment concentrations of in-house C3 and standard C3 were higher than the treatment concentrations of in-house C1 and standard C1 by 6.5-fold and 4.0-fold, respectively. Many previous studies have established that pure curcumin is a selective inhibitor of phosphorylase kinase (39, 40) which inhibits the WT1 protein expressions through PKC signaling pathways (25). Curcumin has also been found to enhance busulfan-induced apoptosis via the downregulation of the expressions of surviving cells in leukemia stem-like KG-1a cells (41). Thus, cell signaling suppression of C3 in LSCs is of enough interest to warrant further investigation.
Related Knowledge Centers
- Cyclic Adenosine Monophosphate
- Enzyme
- Glycogen
- Glycogen Phosphorylase
- Protein Kinase A
- Phosphorylation
- Serine/Threonine-Specific Protein Kinase
- Glucose 1-Phosphate
- Phosphorylase Kinase, Alpha 1
- Phka2