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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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Related in: MedlinePlus

Liquid chromatography (left panel)/electrospray mass spectrometry analyses (right panel) of recombinant non-myristoylated (A) and myristoylated (B) CAP-23/NAP-22. The retention time of myristoylated CAP-23/NAP-22 on the reversed-phase liquid chromatography (left panel of B) was longer than that of non-myristoylated CAP-23/NAP-22 (left panel of A). Each fraction was directly injected into the electrospray mass spectrometry apparatus (right panels). The difference between the observed molecular weights (213.7 Da) corresponded to that of the myristoyl group (210.0 Da).
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fig02: Liquid chromatography (left panel)/electrospray mass spectrometry analyses (right panel) of recombinant non-myristoylated (A) and myristoylated (B) CAP-23/NAP-22. The retention time of myristoylated CAP-23/NAP-22 on the reversed-phase liquid chromatography (left panel of B) was longer than that of non-myristoylated CAP-23/NAP-22 (left panel of A). Each fraction was directly injected into the electrospray mass spectrometry apparatus (right panels). The difference between the observed molecular weights (213.7 Da) corresponded to that of the myristoyl group (210.0 Da).

Mentions: To examine the effects of myristoylation on the interaction of CAP-23/NAP-22 with CaM, two recombinant proteins, i.e., non-myristoylated and myristoylated CAP-23/NAP-22 proteins, were produced in E. coli. For the myristoylated protein, a pBB131 vector (a gift from Dr. J. I. Gordon) containing yeast N-myristoyl transferase cDNA was co-transformed.22,23) Both of its proteins were purified by successive column chromatography on Phenyl-Sepharose and Resource RPC (Amersham Pharmacia Biotech), and the authenticity of the two proteins was established by electrospray mass spectrometry (Fig. 2). The mass of the non-myristoylated protein was determined to be 21,629.2 ± 2.9 Da (the theoretical mass; 21,629.1 Da), while that of the myristoylated protein was 21,839.5 ± 2.0 Da (the theoretical mass; 21,839.5 Da). These results indicated that the two proteins differed only in their N-terminal myristoylation.


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)

Liquid chromatography (left panel)/electrospray mass spectrometry analyses (right panel) of recombinant non-myristoylated (A) and myristoylated (B) CAP-23/NAP-22. The retention time of myristoylated CAP-23/NAP-22 on the reversed-phase liquid chromatography (left panel of B) was longer than that of non-myristoylated CAP-23/NAP-22 (left panel of A). Each fraction was directly injected into the electrospray mass spectrometry apparatus (right panels). The difference between the observed molecular weights (213.7 Da) corresponded to that of the myristoyl group (210.0 Da).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Liquid chromatography (left panel)/electrospray mass spectrometry analyses (right panel) of recombinant non-myristoylated (A) and myristoylated (B) CAP-23/NAP-22. The retention time of myristoylated CAP-23/NAP-22 on the reversed-phase liquid chromatography (left panel of B) was longer than that of non-myristoylated CAP-23/NAP-22 (left panel of A). Each fraction was directly injected into the electrospray mass spectrometry apparatus (right panels). The difference between the observed molecular weights (213.7 Da) corresponded to that of the myristoyl group (210.0 Da).
Mentions: To examine the effects of myristoylation on the interaction of CAP-23/NAP-22 with CaM, two recombinant proteins, i.e., non-myristoylated and myristoylated CAP-23/NAP-22 proteins, were produced in E. coli. For the myristoylated protein, a pBB131 vector (a gift from Dr. J. I. Gordon) containing yeast N-myristoyl transferase cDNA was co-transformed.22,23) Both of its proteins were purified by successive column chromatography on Phenyl-Sepharose and Resource RPC (Amersham Pharmacia Biotech), and the authenticity of the two proteins was established by electrospray mass spectrometry (Fig. 2). The mass of the non-myristoylated protein was determined to be 21,629.2 ± 2.9 Da (the theoretical mass; 21,629.1 Da), while that of the myristoylated protein was 21,839.5 ± 2.0 Da (the theoretical mass; 21,839.5 Da). These results indicated that the two proteins differed only in their N-terminal myristoylation.

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