Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CAPL-A1 and CAPL-A2, two catalytic subunits of Aplysia cAMP-dependent protein kinase, are encoded by mRNAs generated by alternative splicing of transcripts of a gene that contains two mutually exclusive exon cassettes. The subunits are identical except for amino acids 142-183 of the 352 residues, which differ at 10 of 42 positions. CAPL-A1 and CAPL-A2 have now been expressed in insect cells and purified to homogeneity. The subunits differ in their catalytic properties, which have been determined with a series of synthetic peptide substrates. For example, kcat and Km values for the peptide LRRASLG (kemptide) are 42 s-1 and 36 microM and 28 s-1 and 17 microM for CAPL-A1 and CAPL-A2, respectively. CAPL-A1 and CAPL-A2 have different substrate specificities. For example, (kcat/Km)peptide-T/(kcat/Km)kemptide is 9.1 x 10(-3) for CAPL-A1 and 15 x 10(-3) for CAPL-A2, where peptide-T is the kemptide homologue LRRATLG. The subunits also differ in regulation as determined by their interactions with a purified type I regulatory subunit, which has an IC50 for CAPL-A1 that is 3.5 times higher than the IC50 for CAPL-A2. These modest differences reinforce accumulating evidence that the physiological state of a cell depends upon a spectrum of protein kinases with overlapping substrate specificities and regulatory properties.
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PMID:Kinetics and regulation of two catalytic subunits of cAMP-dependent protein kinase from Aplysia californica. 193 53

The amino acid sequences of two catalytic (C) subunits of Aplysia cAMP-dependent protein kinase (cAPK) have been deduced from the nucleotide sequences of cDNAs generated from neuronal poly(A)+ RNA. Both subunits contain 352 residues and are identical except for amino acids 142-183, which differ at 10 out of 42 positions. They derive from alternatively spliced transcripts of a single gene (CAPL) containing two mutually exclusive exon cassettes. CAPL transcripts are present in several classes of identified neurons containing transmitter-sensitive adenylate cyclase, including sensory cells, bag cells, and the left pleural giant cell. Combinatorial expression of the various regulatory (R) and C subunits might produce kinase isoforms with distinct roles in neuronal modulation. Alternatively, holoenzymes with overlapping properties together might contribute to the definition of individual cell types and physiological states.
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PMID:Two catalytic subunits of cAMP-dependent protein kinase generated by alternative RNA splicing are expressed in Aplysia neurons. 248 6

cAMP-dependent protein kinase (PKA) is an important participant in neuronal modulation: the ability of neurons to change their properties in response to external stimuli. In Aplysia mechanosensory neurons, PKA plays roles in both short and long term presynaptic facilitation, which is a simple model for learning and memory. PKA in Aplysia is a collection of structurally and functionally diverse regulatory and catalytic (C) subunits. We have argued that this diversity may in part account for the ability of the enzyme to take part in neuronal events that are spatially and temporally separated. Here, we add credence to this hypothesis by showing that C subunits of Aplysia PKA with alternative N termini target different substrates in subcellular fractions from Aplysia neurons, despite their similar actions on synthetic peptide substrates. Purified recombinant CAPL-AN1A1, which has an N terminus that is homologous to the myristylated sequence described in mammals, catalyzes the formation of two phosphoproteins of 24 and 8 kDa more rapidly than CAPL-AN2A1, which has a distinct N terminus weakly related to that of the yeast TPK1 gene product. The 24-kDa phospoprotein, but not the 8-kDa species, is detected in taxol-stabilized microtubules, suggesting that it is associated with the cytoskeleton. CAPL-AN2A1, in contrast, generates a 55-kDa phosphoprotein that is not observed with CAPL-AN1A1. The 55-kDa species is found in the detergent supernatant of the cytoskeleton fraction. Differential targeting of substrates by C subunits of PKA may therefore contribute to the ability of this kinase to play multiple roles in neuronal modulation.
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PMID:Differential phosphorylation of neuronal substrates by catalytic subunits of Aplysia cAMP-dependent protein kinase with alternative N termini. 808 43