Protein kinase A phosphorylates and regulates dimerization of 14-3-3ζ

Young Mi Gu; Yun Hye Jin; Joong Kook Choi; Kwang Hyun Baek; Chang Yeol Yeo; Kwang Youl Lee

doi:10.1016/j.febslet.2005.12.024

Protein kinase A phosphorylates and regulates dimerization of 14-3-3ζ

Young Mi Gu, Yun Hye Jin, Joong Kook Choi, Kwang Hyun Baek, Chang Yeol Yeo, Kwang Youl Lee

Department of Life Science

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

Recognition of phosphorylated serine/threonine-containing motifs by 14-3-3 depends on the dimerization of 14-3-3. However, the molecular cues that control 14-3-3 dimerization are not well understood. In order to identify proteins that control 14-3-3 dimerization, we analyzed proteins that have effects on 14-3-3 dimerization and report that protein kinase A (PKA) phosphorylates 14-3-3ζ at a specific residue (Ser58). Phosphorylation by PKA leads to modulation of 14-3-3ζ dimerization and affect its interaction with partner proteins. Substitution of Ser58 to Ala completely abolished phosphorylation of 14-3-3ζ by PKA. A phospho-mimic mutant of 14-3-3ζ, Ser58 to Glu substitution, failed to form homodimers, showed reduced interaction with 14-3-3ε and p53, and could not enhance transcriptional activity of p53. Moreover, activation of PKA decreases and inhibition of PKA increases the dimerization of 14-3-3ζ and the functional interaction of 14-3-3ζ with p53. Therefore, our results suggest that PKA is a new member of protein kinases that can phosphorylate and impair the function of 14-3-3.

Original language	English
Pages (from-to)	305-310
Number of pages	6
Journal	FEBS Letters
Volume	580
Issue number	1
DOIs	https://doi.org/10.1016/j.febslet.2005.12.024
State	Published - 9 Jan 2006

Bibliographical note

Funding Information:
This work is supported to by a grant to C.-Y.Y. [C00175 (R08-2003-000-10943-0)] from the Korea Research Foundation and by the Ewha Womans University Research Grants 2003 to C.-Y.Y.

Keywords

14-3-3ζ
Dimerization
Phosphorylation
Protein kinase A

Access to Document

10.1016/j.febslet.2005.12.024

Cite this

@article{b50b53380c01465e95b24d4d652bb71c,

title = "Protein kinase A phosphorylates and regulates dimerization of 14-3-3ζ",

abstract = "Recognition of phosphorylated serine/threonine-containing motifs by 14-3-3 depends on the dimerization of 14-3-3. However, the molecular cues that control 14-3-3 dimerization are not well understood. In order to identify proteins that control 14-3-3 dimerization, we analyzed proteins that have effects on 14-3-3 dimerization and report that protein kinase A (PKA) phosphorylates 14-3-3ζ at a specific residue (Ser58). Phosphorylation by PKA leads to modulation of 14-3-3ζ dimerization and affect its interaction with partner proteins. Substitution of Ser58 to Ala completely abolished phosphorylation of 14-3-3ζ by PKA. A phospho-mimic mutant of 14-3-3ζ, Ser58 to Glu substitution, failed to form homodimers, showed reduced interaction with 14-3-3ε and p53, and could not enhance transcriptional activity of p53. Moreover, activation of PKA decreases and inhibition of PKA increases the dimerization of 14-3-3ζ and the functional interaction of 14-3-3ζ with p53. Therefore, our results suggest that PKA is a new member of protein kinases that can phosphorylate and impair the function of 14-3-3.",

keywords = "14-3-3ζ, Dimerization, Phosphorylation, Protein kinase A",

author = "Gu, {Young Mi} and Jin, {Yun Hye} and Choi, {Joong Kook} and Baek, {Kwang Hyun} and Yeo, {Chang Yeol} and Lee, {Kwang Youl}",

note = "Funding Information: This work is supported to by a grant to C.-Y.Y. [C00175 (R08-2003-000-10943-0)] from the Korea Research Foundation and by the Ewha Womans University Research Grants 2003 to C.-Y.Y.",

year = "2006",

month = jan,

day = "9",

doi = "10.1016/j.febslet.2005.12.024",

language = "English",

volume = "580",

pages = "305--310",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Wiley-Blackwell",

number = "1",

}

TY - JOUR

T1 - Protein kinase A phosphorylates and regulates dimerization of 14-3-3ζ

AU - Gu, Young Mi

AU - Jin, Yun Hye

AU - Choi, Joong Kook

AU - Baek, Kwang Hyun

AU - Yeo, Chang Yeol

AU - Lee, Kwang Youl

N1 - Funding Information: This work is supported to by a grant to C.-Y.Y. [C00175 (R08-2003-000-10943-0)] from the Korea Research Foundation and by the Ewha Womans University Research Grants 2003 to C.-Y.Y.

PY - 2006/1/9

Y1 - 2006/1/9

N2 - Recognition of phosphorylated serine/threonine-containing motifs by 14-3-3 depends on the dimerization of 14-3-3. However, the molecular cues that control 14-3-3 dimerization are not well understood. In order to identify proteins that control 14-3-3 dimerization, we analyzed proteins that have effects on 14-3-3 dimerization and report that protein kinase A (PKA) phosphorylates 14-3-3ζ at a specific residue (Ser58). Phosphorylation by PKA leads to modulation of 14-3-3ζ dimerization and affect its interaction with partner proteins. Substitution of Ser58 to Ala completely abolished phosphorylation of 14-3-3ζ by PKA. A phospho-mimic mutant of 14-3-3ζ, Ser58 to Glu substitution, failed to form homodimers, showed reduced interaction with 14-3-3ε and p53, and could not enhance transcriptional activity of p53. Moreover, activation of PKA decreases and inhibition of PKA increases the dimerization of 14-3-3ζ and the functional interaction of 14-3-3ζ with p53. Therefore, our results suggest that PKA is a new member of protein kinases that can phosphorylate and impair the function of 14-3-3.

AB - Recognition of phosphorylated serine/threonine-containing motifs by 14-3-3 depends on the dimerization of 14-3-3. However, the molecular cues that control 14-3-3 dimerization are not well understood. In order to identify proteins that control 14-3-3 dimerization, we analyzed proteins that have effects on 14-3-3 dimerization and report that protein kinase A (PKA) phosphorylates 14-3-3ζ at a specific residue (Ser58). Phosphorylation by PKA leads to modulation of 14-3-3ζ dimerization and affect its interaction with partner proteins. Substitution of Ser58 to Ala completely abolished phosphorylation of 14-3-3ζ by PKA. A phospho-mimic mutant of 14-3-3ζ, Ser58 to Glu substitution, failed to form homodimers, showed reduced interaction with 14-3-3ε and p53, and could not enhance transcriptional activity of p53. Moreover, activation of PKA decreases and inhibition of PKA increases the dimerization of 14-3-3ζ and the functional interaction of 14-3-3ζ with p53. Therefore, our results suggest that PKA is a new member of protein kinases that can phosphorylate and impair the function of 14-3-3.

KW - 14-3-3ζ

KW - Dimerization

KW - Phosphorylation

KW - Protein kinase A

UR - http://www.scopus.com/inward/record.url?scp=29344452931&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2005.12.024

DO - 10.1016/j.febslet.2005.12.024

M3 - Article

C2 - 16376338

AN - SCOPUS:29344452931

SN - 0014-5793

VL - 580

SP - 305

EP - 310

JO - FEBS Letters

JF - FEBS Letters

IS - 1

ER -

Protein kinase A phosphorylates and regulates dimerization of 14-3-3ζ

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this