Protein kinase isozyme properties

The type I and type II protein kinase isozymes have the same catalytic subunit but different regulatory subunits, which accounts for the differences in their properties (Corbin and Keely, 1977). Protein kinase I is more characteristic of skeletal muscle and easily dissociates into its subunits by interacting with cAMP (Hofman et al., 1975). The type II kinase is more characteristic of bovine heart muscle, and readily dissociates only after the regulatory subunits have been phosphorylated. Type I protein kinse is not phosphorylated by MgATP, but the regulatory subunits of type II protein kinase are rapidly phosphorylated by MgATP (Hofman et al., 1975). 

In addition, vinpocetine selectively inhibits a specific calcium, calmodulin-dependent cycHc nucleotide phosphodiesterase (PDF) isozyme (16). As a result of this inhibition, cycHc guanosine 5 -monophosphate (GMP) levels increase. Relaxation of smooth muscle seems to be dependent on the activation of cychc GMP-dependent protein kinase (17), thus this property may account for the vasodilator activity of vinpocetine. A review of the pharmacology of vinpocetine is available (18). 

Sugimoto T, Itagaki K, Irie K (2008) Design and physicochemical properties of new fluorescent ligands of protein kinase C isozymes focused on CH/7t interaction. Bioorg Med Chem 16 650-657... 

Pseudosubstrate mutant. A mutated form of a protein kinase C isozyme that has three changes in amino acids in the pseudosubstrate sequence is isolated. What properties would you expect this mutated form to have ... 

Isozymes are enzyme variants that catalyze the same reaction but are structurally different (they are coded by separate gene loci). Allozymes are variants that arise due to polymorphism at a single gene locus. Isozymes can vary enormously in their properties (e.g., substrate affinities, responses to allosteric effectors, phosphorylation by protein kinases) to support the different functional needs for a particular reaction in different organs or different compartments of the cell (e.g., mitochon-... 

Proteins that differ somewhat in primary structure and properties from tissue to tissue, but retain essentially the same function, are called tissue-specific isoforms or isozymes. The enzyme creatine kinase is an example of a protein that exists as tissue-specific isozymes, each composed of two subunits with 60 to 72% sequence homology. Of the two creatine kinases that bind to the muscle sarcomere, the M form is produced in skeletal muscle, and the B polypeptide chains are produced in the brain. The protein comprises two subunits, and skeletal muscle therefore produces an MM creatine kinase, and the brain produces a BB form. The heart produces both types of chains and therefore forms a heterodimer, MB, as well as an MM dimer. Two more creatine kinase isozymes are found in mitochondria, a heart mitochondrial creatine kinase, and the universal isoform found in other tissues. (In general, most proteins present in both the mitochondria and cytosol will be present as different isoforms.) The advantage conferred on different tissues by having their own isoform of creatine kinase is unknown. However, tissue-specific isozymes such as MB creatine kinase are useful in diagnosing sites of tissue injury and cell death. 

S Additional information <3, 7> (<3> enzyme exists in different conformational states with different substrate kinetic properties [9] <3> presumably one common nucleoside acceptor site [15] <3> purine deoxynucleo-side activity inseparably associated with deoxycytidine kinase protein [16] <3> several isozymes cytosolic deoxycytidine kinase I and II, plus mitochondrial isozyme [10] <3> multisubstrate enzyme, that also phos-phorylates purine deoxyribonucleotides [9] <7> enzyme has two separate active sites for deoxycytidine and deoxyadenosine activity [22] <3> reacts with both enantiomers of -deoxycytidine, -deoxyguanidine, -deoxyadenosine, and a-D-deoxycytidine is also substrate [31] <3> reacts with both enantiomers of jS-deoxyadenosine, j3-arabinofuranosyl-adenine and jd-deoxyguanine ]34] <3> remarkably relaxed enantioselectivity with respect to cytidine derivatives in p configuration [36] <3> lack of enantioselectivity for D- and L-analogues of cytidine and adenosine [43]) [9, 10, 15, 16, 22, 31, 34, 43]... 

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