Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein Kinase C in its active conformation on the scaffold p62

Li Chun Lisa Tsai; Lei Xie; Kim Dore; Li Xie; Jason C. Del Rio; Charles C. King; Guillermo Martinez-Ariza; Christopher Hulme; Roberto Malinow; Philip E. Bourne; Alexandra C. Newton

doi:10.1074/jbc.M115.676221

Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein Kinase C in its active conformation on the scaffold p62

Li Chun Lisa Tsai
, Lei Xie
, Kim Dore
, Li Xie
, Jason C. Del Rio
, Charles C. King
, Guillermo Martinez-Ariza
, Christopher Hulme
, Roberto Malinow
, Philip E. Bourne
, Alexandra C. Newton

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

35 Scopus citations

Abstract

Background: How atypical PKCs are maintained in an active conformation is unknown. Results: We identify an acidic surface on the aPKC scaffold, p62, that tethers the kinase's autoinhibitory pseudosubstrate to allow activity. The biologically active basic peptide, ZIP, competes for binding to this surface, resulting in localized aPKC autoinhibition. Conclusion: P62 tethers aPKCs in an active conformation. Significance: P62 is a molecular target for ZIP.

Original language	English (US)
Pages (from-to)	21845-21856
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	290
Issue number	36
DOIs	https://doi.org/10.1074/jbc.M115.676221
State	Published - Sep 4 2015

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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Tsai, L. C. L., Xie, L., Dore, K., Xie, L., Del Rio, J. C., King, C. C., Martinez-Ariza, G., Hulme, C., Malinow, R., Bourne, P. E., & Newton, A. C. (2015). Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein Kinase C in its active conformation on the scaffold p62. Journal of Biological Chemistry, 290(36), 21845-21856. https://doi.org/10.1074/jbc.M115.676221

Tsai, LCL, Xie, L, Dore, K, Xie, L, Del Rio, JC, King, CC, Martinez-Ariza, G, Hulme, C, Malinow, R, Bourne, PE & Newton, AC 2015, 'Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein Kinase C in its active conformation on the scaffold p62', Journal of Biological Chemistry, vol. 290, no. 36, pp. 21845-21856. https://doi.org/10.1074/jbc.M115.676221

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title = "Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein Kinase C in its active conformation on the scaffold p62",

abstract = "Background: How atypical PKCs are maintained in an active conformation is unknown. Results: We identify an acidic surface on the aPKC scaffold, p62, that tethers the kinase's autoinhibitory pseudosubstrate to allow activity. The biologically active basic peptide, ZIP, competes for binding to this surface, resulting in localized aPKC autoinhibition. Conclusion: P62 tethers aPKCs in an active conformation. Significance: P62 is a molecular target for ZIP.",

author = "Tsai, \{Li Chun Lisa\} and Lei Xie and Kim Dore and Li Xie and \{Del Rio\}, \{Jason C.\} and King, \{Charles C.\} and Guillermo Martinez-Ariza and Christopher Hulme and Roberto Malinow and Bourne, \{Philip E.\} and Newton, \{Alexandra C.\}",

year = "2015",

month = sep,

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doi = "10.1074/jbc.M115.676221",

language = "English (US)",

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T1 - Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein Kinase C in its active conformation on the scaffold p62

AU - Tsai, Li Chun Lisa

AU - Xie, Lei

AU - Dore, Kim

AU - Xie, Li

AU - Del Rio, Jason C.

AU - King, Charles C.

AU - Martinez-Ariza, Guillermo

AU - Hulme, Christopher

AU - Malinow, Roberto

AU - Bourne, Philip E.

AU - Newton, Alexandra C.

PY - 2015/9/4

Y1 - 2015/9/4

N2 - Background: How atypical PKCs are maintained in an active conformation is unknown. Results: We identify an acidic surface on the aPKC scaffold, p62, that tethers the kinase's autoinhibitory pseudosubstrate to allow activity. The biologically active basic peptide, ZIP, competes for binding to this surface, resulting in localized aPKC autoinhibition. Conclusion: P62 tethers aPKCs in an active conformation. Significance: P62 is a molecular target for ZIP.

AB - Background: How atypical PKCs are maintained in an active conformation is unknown. Results: We identify an acidic surface on the aPKC scaffold, p62, that tethers the kinase's autoinhibitory pseudosubstrate to allow activity. The biologically active basic peptide, ZIP, competes for binding to this surface, resulting in localized aPKC autoinhibition. Conclusion: P62 tethers aPKCs in an active conformation. Significance: P62 is a molecular target for ZIP.

UR - https://www.scopus.com/pages/publications/84941343009

UR - https://www.scopus.com/pages/publications/84941343009#tab=citedBy

U2 - 10.1074/jbc.M115.676221

DO - 10.1074/jbc.M115.676221

M3 - Article

C2 - 26187466

AN - SCOPUS:84941343009

SN - 0021-9258

VL - 290

SP - 21845

EP - 21856

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 36

ER -

Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein Kinase C in its active conformation on the scaffold p62

Abstract

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