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Functional Heterogeneity of Alternatively Spliced Isoforms of Drosophila Ca 2+ /Calmodulin‐Dependent Protein Kinase II
Author(s) -
GuptaRoy Bipasha,
Griffith Leslie C.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66031282.x
Subject(s) - calmodulin , gene isoform , isozyme , biochemistry , biology , function (biology) , enzyme , microbiology and biotechnology , protein kinase a , kinase , chemistry , biophysics , gene
Abstract: The gene for Drosophila calcium/calmodulin‐dependent protein kinase II is alternatively spliced to generate up to 18 different proteins that vary only in a region analogous to the point where mammalian α, β, γ, and δ isozymes show the greatest divergence from each other. To investigate the function of this variable region, we have characterized the catalytic and structural properties of six of the Drosophila isoforms. By several criteria (domain organization, low affinity for calmodulin, holoenzyme structure, and ability to autophosphorylate and become independent of calcium), these proteins are functional homologues of the mammalian calcium/calmodulin‐dependent protein kinase II. Two major isoform‐specific catalytic differences were observed. First, the R3A isoform was found to have a significantly higher K act for calmodulin than the other isoforms. This indicates that the variable region, which is located distal to the calmodulin‐binding domain, may play a role in activation of the enzyme by calmodulin. Decreased sensitivity to calmodulin may be biologically important if free calmodulin is limiting within the neuron. The second catalytic difference noted was that the R6 isoform had a significantly lower K m for the peptide substrate used in this study. Although the variable region is not in the catalytic part of the enzyme, it may have an indirect function in substrate selectivity.