Hyperphosphorylation of JNK-interacting protein 1, a protein associated with Alzheimer disease

Chiara D'Ambrosio, Simona Arena, Gabriella Fulcoli, Meir H. Scheinfeld, Dawang Zhou, Luciano D'Adamio, Andrea Scaloni

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases are activated by pleiotropic signals including environmental stresses, growth factors, and hormones. JNK-interacting protein 1 (JIP1) is a scaffold protein that assembles and facilitates the activation of the mixed lineage kinase-dependent JNK module and also establishes an interaction with β-amyloid precursor protein that has been partially characterized. Here we show that, similarly to other proteins involved in various neurological diseases, JIP1 becomes hyperphosphorylated following activation of stress-activated and MAP kinases. By immobilized metal affinity chromatography and a combined micro-capillary LC/MALDI-TOF/ESI-ion trap mass spectrometry approach, we identified 35 sites of mitotic phosphorylation within JIP1, among which eight were present within (Ser/Thr)-Pro sequence. This motif is modified by various kinases in aggregates of the microtubule-associated protein tau, which generates typical intraneuronal lesions occurring in Alzheimer disease. Most of the post-translational modifications found were located within the JNK, MAP kinase kinase, and RAC-α Ser/Thr protein kinase binding regions; no modifications occurred in protein Src homology 3 and phosphotyrosine interaction domains, which are essential for binding to kinesin, β-amyloid precursor protein, and MAP kinase kinase kinase. Protein phosphorylation is known to affect stability and protein-protein interactions. Thus, the findings that JIP1 is extensively phosphorylated after activation of stress-activated and MAP kinases indicate that these signaling pathways might modulate JIP1 signaling by regulating its stability and association with some, but not all, interacting proteins.

Original languageEnglish (US)
Pages (from-to)97-113
Number of pages17
JournalMolecular and Cellular Proteomics
Volume5
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

JNK Mitogen-Activated Protein Kinases
Alzheimer Disease
Proteins
Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinases
Amyloid beta-Protein Precursor
Phosphorylation
Chemical activation
Phosphotransferases
Kinesin
Phosphotyrosine
Affinity chromatography
Microtubule-Associated Proteins
Protein Stability
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Post Translational Protein Processing
Affinity Chromatography
Protein Binding
Protein Kinases
Growth Hormone

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hyperphosphorylation of JNK-interacting protein 1, a protein associated with Alzheimer disease. / D'Ambrosio, Chiara; Arena, Simona; Fulcoli, Gabriella; Scheinfeld, Meir H.; Zhou, Dawang; D'Adamio, Luciano; Scaloni, Andrea.

In: Molecular and Cellular Proteomics, Vol. 5, No. 1, 01.2006, p. 97-113.

Research output: Contribution to journalArticle

D'Ambrosio, Chiara ; Arena, Simona ; Fulcoli, Gabriella ; Scheinfeld, Meir H. ; Zhou, Dawang ; D'Adamio, Luciano ; Scaloni, Andrea. / Hyperphosphorylation of JNK-interacting protein 1, a protein associated with Alzheimer disease. In: Molecular and Cellular Proteomics. 2006 ; Vol. 5, No. 1. pp. 97-113.
@article{98573e59b34647deaf3e2f4c85673760,
title = "Hyperphosphorylation of JNK-interacting protein 1, a protein associated with Alzheimer disease",
abstract = "The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases are activated by pleiotropic signals including environmental stresses, growth factors, and hormones. JNK-interacting protein 1 (JIP1) is a scaffold protein that assembles and facilitates the activation of the mixed lineage kinase-dependent JNK module and also establishes an interaction with β-amyloid precursor protein that has been partially characterized. Here we show that, similarly to other proteins involved in various neurological diseases, JIP1 becomes hyperphosphorylated following activation of stress-activated and MAP kinases. By immobilized metal affinity chromatography and a combined micro-capillary LC/MALDI-TOF/ESI-ion trap mass spectrometry approach, we identified 35 sites of mitotic phosphorylation within JIP1, among which eight were present within (Ser/Thr)-Pro sequence. This motif is modified by various kinases in aggregates of the microtubule-associated protein tau, which generates typical intraneuronal lesions occurring in Alzheimer disease. Most of the post-translational modifications found were located within the JNK, MAP kinase kinase, and RAC-α Ser/Thr protein kinase binding regions; no modifications occurred in protein Src homology 3 and phosphotyrosine interaction domains, which are essential for binding to kinesin, β-amyloid precursor protein, and MAP kinase kinase kinase. Protein phosphorylation is known to affect stability and protein-protein interactions. Thus, the findings that JIP1 is extensively phosphorylated after activation of stress-activated and MAP kinases indicate that these signaling pathways might modulate JIP1 signaling by regulating its stability and association with some, but not all, interacting proteins.",
author = "Chiara D'Ambrosio and Simona Arena and Gabriella Fulcoli and Scheinfeld, {Meir H.} and Dawang Zhou and Luciano D'Adamio and Andrea Scaloni",
year = "2006",
month = "1",
doi = "10.1074/mcp.M500226-MCP200",
language = "English (US)",
volume = "5",
pages = "97--113",
journal = "Molecular and Cellular Proteomics",
issn = "1535-9476",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "1",

}

TY - JOUR

T1 - Hyperphosphorylation of JNK-interacting protein 1, a protein associated with Alzheimer disease

AU - D'Ambrosio, Chiara

AU - Arena, Simona

AU - Fulcoli, Gabriella

AU - Scheinfeld, Meir H.

AU - Zhou, Dawang

AU - D'Adamio, Luciano

AU - Scaloni, Andrea

PY - 2006/1

Y1 - 2006/1

N2 - The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases are activated by pleiotropic signals including environmental stresses, growth factors, and hormones. JNK-interacting protein 1 (JIP1) is a scaffold protein that assembles and facilitates the activation of the mixed lineage kinase-dependent JNK module and also establishes an interaction with β-amyloid precursor protein that has been partially characterized. Here we show that, similarly to other proteins involved in various neurological diseases, JIP1 becomes hyperphosphorylated following activation of stress-activated and MAP kinases. By immobilized metal affinity chromatography and a combined micro-capillary LC/MALDI-TOF/ESI-ion trap mass spectrometry approach, we identified 35 sites of mitotic phosphorylation within JIP1, among which eight were present within (Ser/Thr)-Pro sequence. This motif is modified by various kinases in aggregates of the microtubule-associated protein tau, which generates typical intraneuronal lesions occurring in Alzheimer disease. Most of the post-translational modifications found were located within the JNK, MAP kinase kinase, and RAC-α Ser/Thr protein kinase binding regions; no modifications occurred in protein Src homology 3 and phosphotyrosine interaction domains, which are essential for binding to kinesin, β-amyloid precursor protein, and MAP kinase kinase kinase. Protein phosphorylation is known to affect stability and protein-protein interactions. Thus, the findings that JIP1 is extensively phosphorylated after activation of stress-activated and MAP kinases indicate that these signaling pathways might modulate JIP1 signaling by regulating its stability and association with some, but not all, interacting proteins.

AB - The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases are activated by pleiotropic signals including environmental stresses, growth factors, and hormones. JNK-interacting protein 1 (JIP1) is a scaffold protein that assembles and facilitates the activation of the mixed lineage kinase-dependent JNK module and also establishes an interaction with β-amyloid precursor protein that has been partially characterized. Here we show that, similarly to other proteins involved in various neurological diseases, JIP1 becomes hyperphosphorylated following activation of stress-activated and MAP kinases. By immobilized metal affinity chromatography and a combined micro-capillary LC/MALDI-TOF/ESI-ion trap mass spectrometry approach, we identified 35 sites of mitotic phosphorylation within JIP1, among which eight were present within (Ser/Thr)-Pro sequence. This motif is modified by various kinases in aggregates of the microtubule-associated protein tau, which generates typical intraneuronal lesions occurring in Alzheimer disease. Most of the post-translational modifications found were located within the JNK, MAP kinase kinase, and RAC-α Ser/Thr protein kinase binding regions; no modifications occurred in protein Src homology 3 and phosphotyrosine interaction domains, which are essential for binding to kinesin, β-amyloid precursor protein, and MAP kinase kinase kinase. Protein phosphorylation is known to affect stability and protein-protein interactions. Thus, the findings that JIP1 is extensively phosphorylated after activation of stress-activated and MAP kinases indicate that these signaling pathways might modulate JIP1 signaling by regulating its stability and association with some, but not all, interacting proteins.

UR - http://www.scopus.com/inward/record.url?scp=31644451099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31644451099&partnerID=8YFLogxK

U2 - 10.1074/mcp.M500226-MCP200

DO - 10.1074/mcp.M500226-MCP200

M3 - Article

VL - 5

SP - 97

EP - 113

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

SN - 1535-9476

IS - 1

ER -