Rvs. Raju et al., BIOLOGICAL SIGNIFICANCE OF PHOSPHORYLATION AND MYRISTOYLATION IN THE REGULATION OF CARDIAC-MUSCLE PROTEINS, Molecular and cellular biochemistry, 176(1-2), 1997, pp. 135-143
Post-translational modification has long been recognized as a way in w
hich the properties of proteins may be subtly altered after synthesis
of the polypeptide chain is complete. Amongst the moieties most common
ly encountered covalently attached to proteins are oligosaccharides, p
hosphate, acetyl, formyl and nucleosides. Protein phosphorylation and
dephosphorylation is one of the most prevalent and best understood mod
ifications employed in cellular regulation. The bovine heart calmoduli
n-dependent cyclic nucleotide phosphodiesterase (CaMPEDE) can be phosp
horylated by cAMP-dependent protein kinase, resulting in a decrease in
the enzyme's affinity for Ca2+ and calmodulin (CaM). The phosphorylat
ion of CaMPDE is blocked by Ca2+ and CaM and reversed by the CaM-depen
dent phosphatase (calcineurin). The dephosphorylation is accompanied b
y an increase in the affinity of the phosphodiesterase for CaM. Analys
is of the complex regulatory properties of CaMPDE has led to the sugge
stion that fluxes of cAMP and Ca2+ during cell activations are closely
coupled and that the CaMPDE play a key role in the signal coupling ph
enomenon. The high molecular weight calmodulin binding protein (HMWCaM
BP) was phosphorylated by cAMP-dependent protein kinase. Phosphorylati
on of HMWCBP was higher in the absence of Ca2+/CaM then in the presenc
e of Ca2+/CaM and reversed by the CaM-dependent phosphatase. Recently,
it has become apparent that the binding of myristate to proteins is a
lso widespread in eukaryotic cells and viruses and certainly is of gre
at importance to the correct functioning of an organism. Myristoyl CoA
:protein N-myristoyltransferase (NMT) catalyses the attachment of myri
state to the amino-terminal glycine residue of various signal transduc
tion proteins. Cardiac tissue express high levels of cAMP-dependent pr
otein kinase whose catalytic subunit is myristoylated. The subcellular
localization of bovine cardiac muscle NMT indicated a majority of the
activity was localized in cytoplasm. Under native conditions the enzy
me exhibited an apparent molecular mass of 50 kDa. Recovery of NMT act
ivity, from both cytosol and particulate fractions, was found to be hi
gher than the total activity in crude homogenates, suggesting that par
ticulate fraction may contain an inhibitory activity towards NMT. Rese
arch in our laboratory has been focusing on the covalent modification
of proteins and regulation of various signal transduction proteins. Th
is special review is designed to summarize some aspects of the current
work on co- and post-translational modification of proteins in cardia
c muscle.