Evolution of the Creatine Kinases

Abstract

In both mammals and birds, the creatine kinase (CK) family consists of four types of genes: cytosolic brain type (B-CK); cytosolic muscle type (M-CK); mitochondrial ubiquitous, acidic type (Mi a -CK); and mitochondrial sarcomeric, basic type (Mi b -CK). We report here the cloning of the chicken Mi a -CK cDNA and its gene. Amino acid sequences of the mature chicken Mi-CK proteins show about 90% identity to the homologous mammalian isoforms. The leader peptides, however, which are isoenzyme-specifically conserved among the mammalian Mi-CKs, are quite different in the chicken with amino acid identity values compared with the mammalian leader peptides of 38.5-51.3%.The chicken Mi a -CK gene spans about 7.6 kilobases and contains 9 exons. The region around exon 1 shows a peculiar base composition, with more than 80% GC, and has the characteristics of a CpG island. The upstream sequences lack TATA or CCAAT boxes and display further properties of housekeeping genes. Several transcription factor binding sites known from mammalian Mi-CK genes are absent from the chicken gene. Although the promoter structure suggests a ubiquitous range of expression, analysis of Mi a -CK transcripts in chicken tissues shows a restricted pattern and therefore does not fulfill all criteria of a housekeeping enzyme.A sufficient capacity and balanced regulation of "high energy phosphate" supply and turnover is essential for the proper function of any cell. Large amounts of energy-rich phosphagens can be found in many cells or tissues throughout the animal kingdom. In all vertebrates and also in some invertebrates this phosphagen is phosphorylcreatine (PCr) 1 (1). PCr and ADP are the products of the reversible transfer of ␥-phosphate groups from ATP to creatine, catalyzed by the creatine kinases (CKs). Two fundamental types of CKs can be found in vertebrates: cytosolic and mitochondrial CKs. The subcellular localization, the biochemical and kinetic data, and the loss of flagellar motility in spermatozoa upon inhibition of the CK system and other data (for review, see Ref.2) led to the suggestion of a metabolic PCr circuit with PCr as a transport and storage form of high energy phosphate. The PCr circuit connects sites of high energy phosphate production (glycolysis and oxidative phosphorylation) with those of high energy phosphate consumption. At the producing end of the circuit, CK is thought to have privileged access to ATP generated either by glycoclysis or by oxidative phosphorylation in the mitochondrial matrix and uses this ATP to generate PCr. At the receiving end, CK is functionally coupled to various ATPases (for instance myosin ATPase of myofibrils), which use the ATP generated in the reverse CK reaction.In chicken there are five different CK subunits known so far; three are found in the cytosol, two in mitochondria. The cytosolic subunits are called M-CK (muscle) and B a -CK and B b -CK (brain, more acidic and more basic, respectively) and can dimerize with each other (3-5). They are found soluble in the cytosol, but fractions are a...

Arginine Kinase Expression and Localization in Growth Cone Migration

“…Both phosphotransferases belong to a family that is so highly conserved that functional hybrid enzymes can be formed (Reddy and Watts, 1994). Vertebrates have four CK genes that encode tissue-specific isozymes (Wallimann, 1994;Muhlebach et al, 1996). Although echinoderms and annelids can express both CK and argK (Thoai and Robin, 1964;Moreland et al, 1967), only argK has been reported in arthropods (Wallimann and Eppenberger, 1973).…”