Current Proteomics

Bernd Rehm  
Institute of Molecular BioSciences Massey University
Private Bag 11222
Palmerston North
New Zealand

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Novel Intracellular Signaling Mechanism Revealed by Functional Analyses of Myristoyl Moiety of NAP22 and a Comprehensive Analysis of Nα-Myristoylated Proteins

Author(s): Nobuhiro Hayashi.

Abstract:

Mass spectrometry has shown that NAP22, a neuron specific protein isolated from rat brain is myristoylated, and it was additionally demonstrated by physicochemical methods that the myristoylation functioning in tandem with the phospholipid membrane is also directly involved in the interaction with calmodulin. Furthermore, besides the myristoylated brain specific protein, Src kinase and the HIV nef gene product have been shown to interact with calmodulin in the same way. Interestingly, phosphorylation of the myristoylated proteins abolishes their interaction with calmodulin. Structural and functional studies have revealed that, besides the necessary conditions for myristoylation, the interaction requires certain additional conditions such as the co-existence of basic amino acid residues in the myristoylated domain. Thus, myristoylated proteins in cells regulate signal transduction between the membrane and cytoplasmic fractions. An algorithm we have developed to find myristoylated proteins in cells predicts hundreds of myristoylated proteins. Interestingly, a large portion of the myristoylated proteins supposed to take part in the signal transduction between the membrane and cytoplasmic fractions, such as NAP22 , are included in the the predicted myristoylated proteins. If the proteins functionally regulated by the posttranslational protein modification myristoylation are understood as cross-talk points within the intracellular signal transduction system, the known signaling pathways can be linked with each other, and a novel map of this intracellular network constructed.

Keywords: Myristoylation, intracellular signaling system, calmodulin, NAP22, HIV Nef, Src, MARCKS, membrane microdomain

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Article Details

VOLUME: 4
ISSUE: 3
Year: 2007
Page: [162 - 173]
Pages: 12
DOI: 10.2174/157016407783221330
Price: $58