Abstract
We report the identification and characterization of JAMP (JNK1 [Jun N-terminal kinase 1]-associated membrane protein), a predicted seven-transmembrane protein that is localized primarily within the plasma membrane and associates with JNK1 through its C-terminal domain. JAMP association with JNK1 outcompetes JNK1 association with mitogen-activated protein kinase phosphatase 5, resulting in increased and prolonged JNK1 activity following stress. Elevated expression of JAMP following UV or tunicamycin treatment results in sustained JNK activity and a higher level of JNK-dependent apoptosis. Inhibition of JAMP expression by RNA interference reduces the degree and duration of JNK activation and concomitantly the level of stress-induced apoptosis. Through its regulation of JNK1 activity, JAMP emerges as a membrane-anchored regulator of the duration of JNK1 activity in response to diverse stress stimuli.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Apoptosis
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Carrier Proteins / biosynthesis
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Carrier Proteins / physiology*
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Cell Line
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Cell Line, Tumor
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Cell Membrane / metabolism*
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Cell Movement
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DNA / metabolism
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DNA, Complementary / metabolism
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Dual-Specificity Phosphatases
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Gene Expression Regulation, Enzymologic*
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Glycosylation
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Humans
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Immunoprecipitation
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MAP Kinase Signaling System
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / physiology*
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Mice
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Microscopy, Confocal
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Molecular Sequence Data
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NIH 3T3 Cells
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Phosphoprotein Phosphatases / metabolism
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Protein Binding
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Protein Structure, Tertiary
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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Subcellular Fractions / metabolism
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Time Factors
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Tissue Distribution
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Transfection
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Tunicamycin / pharmacology
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Ultraviolet Rays
Substances
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Carrier Proteins
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DNA, Complementary
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JAMP protein, mouse
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Membrane Glycoproteins
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Tunicamycin
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Green Fluorescent Proteins
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DNA
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Dusp10 protein, mouse
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Phosphoprotein Phosphatases
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Dual-Specificity Phosphatases