HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M500226-MCP200v1 5/1/97    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Glossary Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by D’Ambrosio, C. Articles by Scaloni, A. Search for Related Content PubMed PubMed Citation Articles by D’Ambrosio, C. Articles by Scaloni, A. Social Bookmarking                      What's this?

Molecular & Cellular Proteomics 5:97-113, 2006.
© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Research

Hyperphosphorylation of JNK-interacting Protein 1, a Protein Associated with Alzheimer Disease^*,S

Chiara D’Ambrosio^,, Simona Arena^,, Gabriella Fulcoli^,, Meir H. Scheinfeld^¶, Dawang Zhou^¶, Luciano D’Adamio^¶,|| and Andrea Scaloni^,**

From the Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Naples, Italy, ^¶ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, and ^|| Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Ceinge Biotecnologie Avanzate, 80145 Naples, Italy

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 ß-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 microcapillary 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- 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, ß-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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Nihalani, H. Wong, R. Verma, and L. B. Holzman Src Family Kinases Directly Regulate JIP1 Module Dynamics and Activation Mol. Cell. Biol., April 1, 2007; 27(7): 2431 - 2441. [Abstract] [Full Text] [PDF]

				G. Caratu, D. Allegra, M. Bimonte, G. G. Schiattarella, C. D'Ambrosio, A. Scaloni, M. Napolitano, T. Russo, and N. Zambrano Identification of the Ligands of Protein Interaction Domains through a Functional Approach Mol. Cell. Proteomics, February 1, 2007; 6(2): 333 - 345. [Abstract] [Full Text] [PDF]

				M. A. Bogoyevitch and B. Kobe Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 1061 - 1095. [Abstract] [Full Text] [PDF]