Myristoylation of the dual-specificity phosphatase c-JUN N-terminal kinase (JNK) stimulatory phosphatase 1 is necessary for its activation of JNK signaling and apoptosis

Schwertassek, U., Buckley, D. A., Xu, C. F., Lindsay, A. J., McCaffrey, M. W., Neubert, T. A., Tonks, N. K. (June 2010) Myristoylation of the dual-specificity phosphatase c-JUN N-terminal kinase (JNK) stimulatory phosphatase 1 is necessary for its activation of JNK signaling and apoptosis. Febs Journal, 277 (11). pp. 2463-2473. ISSN 1742-464X

URL: http://www.ncbi.nlm.nih.gov/pubmed/20553486
DOI: 10.1111/j.1742-4658.2010.07661.x

Abstract

Activation of the c-JUN N-terminal kinase (JNK) pathway is implicated in a number of important physiological processes, from embryonic morphogenesis to cell survival and apoptosis. JNK stimulatory phosphatase 1 (JSP1) is a member of the dual-specificity phosphatase subfamily of protein tyrosine phosphatases. In contrast to other dual-specificity phosphatases that catalyze the inactivation of mitogen-activated protein kinases, expression of JSP1 activates JNK-mediated signaling. JSP1 and its relative DUSP15 are unique among members of the protein tyrosine phosphatase family in that they contain a potential myristoylation site at the N-terminus (MGNGMXK). In this study, we investigated whether JSP1 was myristoylated and examined the functional consequences of myristoylation. Using mass spectrometry, we showed that wild-type JSP1, but not a JSP1 mutant in which Gly2 was mutated to Ala (JSP1-G2A), was myristoylated in cells. Although JSP1 maintained intrinsic phosphatase activity in the absence of myristoylation, the subcellular localization of the enzyme was altered. Compared with the wild type, the ability of nonmyristoylated JSP1 to induce JNK activation and phosphorylation of the transcription factor c-JUN was attenuated. Upon expression of wild-type JSP1, a subpopulation of cells, with the highest levels of the phosphatase, was induced to float off the dish and undergo apoptosis. In contrast, cells expressing similar levels of JSP1-G2A remained attached, further highlighting that the myristoylation mutant was functionally compromised.

Item Type: Paper
Uncontrolled Keywords: apoptosis JNK JSP1 myristoylation phosphatase PROTEIN-TYROSINE PHOSPHATASES TRANSDUCTION PHOSPHORYLATION PATHWAYS INFLAMMATION INHIBITORS LMW-DSP2 INSULIN UPDATE CANCER
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Tonks lab
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: CSHL Librarian
Date: June 2010
Date Deposited: 19 Oct 2011 16:21
Last Modified: 30 Dec 2014 17:10
PMCID: PMC2894504
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15523

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