JAMP, a Jun N-terminal kinase 1 (JNK1)-associated membrane protein, regulates duration of JNK activity.
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.
Kadoya
Takayuki
T
Signal Transduction Program, The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Khurana
Ashwani
A
Tcherpakov
Marianna
M
Bromberg
Kenneth D
KD
Didier
Christine
C
Broday
Limor
L
Asahara
Toshimasa
T
Bhoumik
Anindita
A
Ronai
Ze'ev
Z
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D054637:Dual-Specificity Phosphatases; D015971:Gene Expression Regulation, Enzymologic; D006031:Glycosylation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D014415:Tunicamycin / Q000494:pharmacology; D014466:Ultraviolet Rays
D002352:Carrier Proteins; D018076:DNA, Complementary; C505618:JAMP protein, mouse; D008562:Membrane Glycoproteins; D014415:Tunicamycin; D049452:Green Fluorescent Proteins; D004247:DNA; C505617:Dusp10 protein, mouse; D010749:Phosphoprotein Phosphatases; D054637:Dual-Specificity Phosphatases