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N-myristoylated proteins, key components in intracellular signal transduction systems enabling rapid and flexible cell responses.

Hayashi N, Titani K - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions.Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins.On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama-shi, Kanagawa Pref., 226-8501, Japan. nhayashi@bio.titech.ac.jp

ABSTRACT
N-myristoylation, one of the co- or post-translational modifications of proteins, has so far been regarded as necessary for anchoring of proteins to membranes. Recently, we have revealed that N(alpha)-myristoylation of several brain proteins unambiguously regulates certain protein-protein interactions that may affect signaling pathways in brain. Comparison of the amino acid sequences of myristoylated proteins including those in other organs suggests that this regulation is involved in signaling pathways not only in brain but also in other organs. Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions. An algorithm we have developed to identify myristoylated proteins in cells predicts the presence of hundreds of myristoylated proteins. Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins. If the proteins functionally regulated by myristoylation, a posttranslational protein modification, were understood as cross-talk points within the intracellular signal transduction system, known signaling pathways could thus be linked to each other, and a novel map of this intracellular network could be constructed. On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

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Scheme of reversible translocation of myristoylated proteins between the membrane and cytoplasmic fractions.
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fig09: Scheme of reversible translocation of myristoylated proteins between the membrane and cytoplasmic fractions.

Mentions: Because of the reversibility of these transitions, they are considered to play a role in communications between membranes and cytoplasmic fractions. Recently, some reports have shown that myristoylated proteins exist in membrane micro domains, called rafts,48) and they are thought to function for processing the signals rapidly and flexibly. Therefore, myristoylated proteins may be designed as multi-functional molecules. Figure 9 shows a summary of reversible translocations of myristoylated proteins between membranes and cytoplasmic fractions under the regulation of signaling system crosstalks. Phosphorylation of myristoylated proteins abolishes their interactions with CaM, and it might also reduce their affinities to membranes because of the introduction of negative charges. Their interactions with CaM might also inhibit their localization to membranes because CaM which binds directly to the myristoyl moiety is essential for the membrane binding by serving as a membrane anchor. The state of membranes may also have effects on their interactions. Some myristoylated proteins have been reported to localize transiently to membrane micro-domains according to the state of cells.49)


N-myristoylated proteins, key components in intracellular signal transduction systems enabling rapid and flexible cell responses.

Hayashi N, Titani K - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Scheme of reversible translocation of myristoylated proteins between the membrane and cytoplasmic fractions.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108300&req=5

fig09: Scheme of reversible translocation of myristoylated proteins between the membrane and cytoplasmic fractions.
Mentions: Because of the reversibility of these transitions, they are considered to play a role in communications between membranes and cytoplasmic fractions. Recently, some reports have shown that myristoylated proteins exist in membrane micro domains, called rafts,48) and they are thought to function for processing the signals rapidly and flexibly. Therefore, myristoylated proteins may be designed as multi-functional molecules. Figure 9 shows a summary of reversible translocations of myristoylated proteins between membranes and cytoplasmic fractions under the regulation of signaling system crosstalks. Phosphorylation of myristoylated proteins abolishes their interactions with CaM, and it might also reduce their affinities to membranes because of the introduction of negative charges. Their interactions with CaM might also inhibit their localization to membranes because CaM which binds directly to the myristoyl moiety is essential for the membrane binding by serving as a membrane anchor. The state of membranes may also have effects on their interactions. Some myristoylated proteins have been reported to localize transiently to membrane micro-domains according to the state of cells.49)

Bottom Line: Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions.Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins.On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama-shi, Kanagawa Pref., 226-8501, Japan. nhayashi@bio.titech.ac.jp

ABSTRACT
N-myristoylation, one of the co- or post-translational modifications of proteins, has so far been regarded as necessary for anchoring of proteins to membranes. Recently, we have revealed that N(alpha)-myristoylation of several brain proteins unambiguously regulates certain protein-protein interactions that may affect signaling pathways in brain. Comparison of the amino acid sequences of myristoylated proteins including those in other organs suggests that this regulation is involved in signaling pathways not only in brain but also in other organs. Thus, it has been shown that myristoylated proteins in cells regulate the signal transduction between membranes and cytoplasmic fractions. An algorithm we have developed to identify myristoylated proteins in cells predicts the presence of hundreds of myristoylated proteins. Interestingly, a large portion of the myristoylated proteins thought to take part in signal transduction between membranes and cytoplasmic fractions are included in the predicted myristoylated proteins. If the proteins functionally regulated by myristoylation, a posttranslational protein modification, were understood as cross-talk points within the intracellular signal transduction system, known signaling pathways could thus be linked to each other, and a novel map of this intracellular network could be constructed. On the basis of our recent results, this review will highlight the multifunctional aspects of protein N-myristoylation in brain.

Show MeSH
Related in: MedlinePlus