Threonine muscle

The a subunits, for which two isoforms exist in mammals (al, a2), contain conventional protein serine/threonine kinase domains at the N-terminus, with a threonine residue in the activation loop (Thr-172) that must be phosphorylated by upstream kinases (see below) before the kinase is active. The kinase domain is followed by an autoinhibitory domain, whose effect is somehow relieved by interaction with the other subunits. The C-terminal domain of the a subunit is required for the formation of a complex with the C-terminal domain of the (3 subunit, which in turn mediates binding to the y subunit. The al and a2 catalytic subunit isoforms are widely distributed, although a2 is most abundant in muscle and may be absent in cells of the endothelial/hemopoietic lineage. 

Nakielny, S., Cohen, P., Wu, J., and Sturgill, T. (1992a). MAP kinase activator from insulin-stimulated skeletal muscle is a protein serine/threonine kinase. EMBO S. 11 2123-2129. 

Serine/threonine kinase activity has been reported in ESP of pepsin-HCl isolated muscle larvae (Arden el al., 1997) and kinase activity was associated with proteins of 70 and 135 kDa. Phosphorylation status is functionally significant for multiple regulatory factors, including those involved in muscle differentiation (Li et al., 1992). Therefore, kinase activity in parasite secretions may be significant in either the muscle or intestinal phases of infection. 

The diacylglycerols released by phospholipase C diffuse laterally through the bilayer and, together with the incoming Ca2+, activate protein kinases C. These kinases also require phosphatidylserine for their activity and phosphorylate serine and threonine side chains in a variety of proteins.329 330b They are stimulated by the released unsaturated diacylglycerols. In addition protein kinases C can be activated by phorbol esters, which are the best known tumor promoters (Box 11-D). The diacylglycerol requirement favors a function for these protein kinases in membranes. They also appear to cooperate with calmodulin to activate the Ca2+-dependent contraction of smooth muscle.330... 

Activation of phospholipase C leads to cleavage of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG). 1P3 promotes release of Ca2+ from storage organelles, whereby contraction of smooth muscle cells, breakdown of glycogen, or exocytosis may be initiated. DAG stimulates protein kinase C, which phosphorylates certain serine- or threonine-containing enzymes. 

Neuromotor disorders, including paresthesia of the hands and feet, hyperactive deep tendon reflexes and muscle weakness. These can be explained by the role of acetyl CoA in the synthesis of the neurotransmitter acetylcholine and the impaired formation of threonine acyl esters in myelin. Dysmyelination may explain the persistence and recurrence of neurological problems many years after nutritional rehabilitation in people who had suffered from burning foot syndrome. 

Potassium is a cofactor and activates a large variety of enzymes, including glycerol dehydrogenase, pyruvate kinase, L-threonine dehydrase, and ATPase. Its acute toxicity is primarily due to its action as an electrolyte. Excessive or diminished potassium levels can disrupt membrane excitability and influence muscle cell contractility and neuronal excitability. 

Protein kinase C (PKC) may play a role in tonic tension. PKC refers to a family of related serine/threonine kinases, five of which are found in smooth muscle. PKC is activated by diacylglycerol, or DAG. DAG (and also IP3) is liberated from membranes by the action of phospholipase C (PLC) on phosphatidylinositol 4,5-bisphosphate, or by the action of phospholipase D (PLD) on phosphatidylcholine. A number of receptor-mediated events are transduced by activation of these lipases. Some agents that elicit tonic contraction (e.g., angiotensin II) activate PLD, thus producing DAG (but not IP3), which activates PKC with no effect on [Ca +]j. There are at least three sites on LC20 that can be phosphorylated by PKC, but it is not known which one, if any, of these is involved in the induction of contraction and latch. 

Myotonic dystrophy (Steinert s disease) Muscle stiffness and impaired relaxation after contraction, wasting of muscles of face, neck, distal limbs, many other serious symptoms. Defect in gene coding for a serine-threonine kinase, resulting in impaired Na-K ATPase activity and perhaps other problems. 

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