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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular signals are transduced into cells through mitogen-activated protein kinases (MAPKs), which are activated by their upstream kinases. Recently, families of scaffolding proteins have been identified to tether specific combinations of these kinases along specific signaling pathways. Here we describe a protein, JLP (c-Jun NH2-terminal kinase-associated leucine zipper protein), which acts as a scaffolding protein to bring together Max and c-Myc along with JNK (c-Jun NH2-terminal kinase) and p38MAPK, as well as their upstream kinases MKK4 (MAPK kinase 4) and MEKK3 (MAPK kinase kinase 3). Thus, JLP defines a family of scaffolding proteins that bring MAPKs and their target transcription factors together for the execution of specific signaling pathways.
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PMID:JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors. 1239 7

Previously, we cloned and sequenced a novel human sperm associated antigen 9 (SPAG9). Northern blot analysis and RNA in situ hybridization experiments revealed testis- and stage-specific expression of SPAG9 mRNA, mainly confined to round spermatid suggesting haploid germ cell expression Studies on the human and non-human primates (macaque and baboon) have shown a homology of 84.9% and 90.6% at amino acid level and 94% and 96.8% at DNA level, respectively. The presence of high level of homology at amino acid and DNA level indicates that SPAG9 is conserved in human, baboon and macaque sharing common function and common origin in the biological past. In addition, SPAG9 protein revealed structural homology with c-Jun NH2-terminal kinase (JNK) interacting protein (JIP). The amino acid sequence analysis of SPAG9 predicted coiled coil, leucine zipper and transmembrane domain, speculating the involvement of SPAG9 mediated signal transduction pathways in reproductive processes.
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PMID:Sperm associated antigen 9 (SPAG9): a new member of c-Jun NH2 -terminal kinase (JNK) interacting protein exclusively expressed in testis. 1607 55

The specific and efficient activation of mitogen-activated protein kinase (MAPK) signaling modules is mediated, at least in part, by scaffold proteins. c-Jun NH(2)-terminal kinase (JNK)-associated leucine zipper protein (JLP) was identified as a scaffold protein for JNK and p38 MAPK signaling modules. JLP is expressed nearly ubiquitously and is involved in intracellular signaling pathways, such as the G(alpha13) and Cdo-mediated pathway, in vitro. To date, however, JLP expression has not been analyzed in detail, nor are its physiological functions well understood. Here we investigated the expression of JLP in the mouse testis during development. Of the tissues examined, JLP was strongest in the testis, with the most intense staining in the elongated spermatids. Since the anti-JLP antibody used in this study can recognize both JLP and sperm-associated antigen 9 (SPAG9), a splice variant of JLP that has been studied extensively in primates, we also examined its expression in macaque testis samples. Our results indicated that in mouse and primate testis, the isoform expressed at the highest level was JLP, not SPAG9. We also investigated the function of JLP by disrupting the Jlp gene in mice, and found that the male homozygotes were subfertile. Taken together, these observations may suggest that JLP plays an important role in testis during development, especially in the production of functionally normal spermatozoa.
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PMID:Ablation of the scaffold protein JLP causes reduced fertility in male mice. 1857 3

Scaffold proteins for MAP kinase (MAPK) signalling modules play an important role in the specific and efficient signal transduction of the relevant MAPK cascades. Here, we investigated the function of the scaffolding protein c-Jun NH(2)-terminal kinase (JNK)-associated leucine zipper protein (JLP) by depleting it in cultured cells using a short hairpin RNA (shRNA) against human JLP. HeLa and DLD-1 cells stably expressing the shRNA showed a defect in cell migration. The re-expression of full-length shRNA-resistant mouse JLP rescued the impaired cell migration of the JLP-depleted HeLa cells; whereas, a C-terminal deletion mutant of mouse JLP, which failed to bind the G protein G(alpha13), showed little or no effect on the cell migration defect. Furthermore, although a constitutively active G(alpha13) enhanced the migration of control HeLa cells, the G(alpha13)-induced cell migration was significantly suppressed in the JLP-depleted HeLa cells. Taken together, these results suggest that JLP regulates cell migration through an interaction with G(alpha13).
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PMID:The scaffold protein c-Jun NH2-terminal kinase-associated leucine zipper protein regulates cell migration through interaction with the G protein G(alpha 13). 1882 71

Oxidative stress, which can be caused by an overproduction of reactive oxygen species (ROS), often leads to cell death. In recent years, c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP, also known as SPAG9 or JIP4), a scaffold protein for JNK mitogen-activated protein kinase (MAPK) signaling pathways, was found to serve as a novel biomarker for cancer. However, although JNK MAPK pathways are reported to be activated in response to various stimuli, including oxidative stress, whether JLP is involved in ROS signaling remains unknown. In this study, we examined the role of JLP in hydrogen peroxide (H2O2)-induced cancer cell death, and found that JLP knockdown (KD) cells exhibit a substantially enhanced cell death response, along with increased intracellular ROS levels. This is the first demonstration of a protective role for JLP in response to cell-death stimulation. We also found that the H2O2-induced JNK activation was attenuated in JLP KD cancer cells. The decreases in cell viability and JNK activation in the JLP KD cells were almost completely reversed by expressing wild-type JLP, but not a mutant JLP lacking the JNK-binding domain. These data collectively suggest that the JLP-JNK signaling pathway counteracts ROS-induced cancer cell death.
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PMID:JLP-JNK signaling protects cancer cells from reactive oxygen species-induced cell death. 2975 43

Previous studies have established the antitumor activity of curcumin, a major component of turmeric. Increasing evidence indicates that curcumin induces autophagy, the activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathways, and reactive oxygen species (ROS)-mediated cell death. The c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP), a scaffold protein for MAPK signaling pathways, has been identified as a candidate biomarker for cancer. In this study, we explored the role of JLP in curcumin-induced cancer cell death. We found that JLP knockdown (KD) increases cell death and intracellular ROS levels. Furthermore, JLP KD impaired lysosomal accumulation around perinuclear regions, which led to the inhibition of autophagosome-lysosome fusion, and attenuated p38 MAPK activation in curcumin-treated cells. The decreases in cell viability and p38 MAPK activation were reversed by expressing wild-type JLP but not a JLP mutant lacking the p38 MAPK-binding domain. In addition, the inactivation of a key gene involved in autophagy increased sensitivity to curcumin-induced cell death. Together, these results suggest that JLP mediates the induction of autophagy by regulating lysosome positioning and p38 MAPK signaling, indicating an overall protective role in curcumin-induced ROS-mediated cancer cell death.
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PMID:Protective role of c-Jun NH2-terminal kinase-associated leucine zipper protein (JLP) in curcumin-induced cancer cell death. 3178 36