Genomes and Genes
Gene Symbol: Mapk9
Description: mitogen-activated protein kinase 9
Alias: SAPK, mitogen-activated protein kinase 9, MAP kinase 9, MAPK 9, SAPK-alpha, c-Jun N-terminal kinase 2, p54-alpha, stress activated protein kinase alpha II, stress-activated protein kinase JNK2
- Katz S, Boland R, Santillan G. Purinergic (ATP) signaling stimulates JNK1 but not JNK2 MAPK in osteoblast-like cells: contribution of intracellular Ca2+ release, stress activated and L-voltage-dependent calcium influx, PKC and Src kinases. Arch Biochem Biophys. 2008;477:244-52 pubmed publisher..8 cells in a way dependent on PI-PLC/IP(3)/intracellular Ca(2+) release and Ca(2+) influx through stress activated and L-type voltage-dependent calcium channels and involves PKC and Src kinases. ..
- Guan Z, Buckman S, Miller B, Springer L, Morrison A. Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. J Biol Chem. 1998;273:28670-6 pubmed..We reported previously that IL-1beta rapidly activates the c-Jun NH2-terminal/stress-activated protein kinases (JNK/SAPK) and p38 mitogen-activated protein kinase (MAPK) and also induces Cox-2 expression and prostaglandin E2 (PGE2) ..
- Lian S, Xia Y, Khoi P, Ung T, Yoon H, Kim N, et al. Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-ÐºB, and AP-1 pathways in human endothelial cells. Toxicology. 2015;338:104-16 pubmed publisher..These results demonstrated that Cd induces MMP-9 expression via ROS-dependent EGFR->Erk1/2, JNK1/2->AP-1 and EGFR->Akt->NF-ÎºB signaling pathways and, in turn, stimulates invasiveness in human endothelial cells. ..
- Wang X, Pei D, Xu J, Guan Q, Sun Y, Liu X, et al. Opposing effects of Bad phosphorylation at two distinct sites by Akt1 and JNK1/2 on ischemic brain injury. Cell Signal. 2007;19:1844-56 pubmed
- Kurokawa M, Mitani K, Yamagata T, Takahashi T, Izutsu K, Ogawa S, et al. The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death. EMBO J. 2000;19:2958-68 pubmed..Evi-1 blocks cell death by selectively inhibiting JNK, thereby contributing to oncogenic transformation of cells. ..
- De Graeve F, Bahr A, Sabapathy K, Hauss C, Wagner E, Kedinger C, et al. Role of the ATFa/JNK2 complex in Jun activation. Oncogene. 1999;18:3491-500 pubmed..1996), is not a substrate for this kinase in vivo but, instead, serves as a JNK2-docking site for ATFa-associated partners like JunD, allowing them to be phosphorylated by the bound kinase. ..
- Butterfield L, Zentrich E, Beekman A, Heasley L. Stress- and cell type-dependent regulation of transfected c-Jun N-terminal kinase and mitogen-activated protein kinase kinase isoforms. Biochem J. 1999;338 ( Pt 3):681-6 pubmed..These findings indicate selective activation of JNK and MKK isoforms in a manner that is dependent upon the specific cell stress and the cell type. ..
- Vesely D. New anticancer agents: hormones made within the heart. Anticancer Res. 2012;32:2515-21 pubmed..In addition to inhibiting these mitogen-activated protein kinases (MAPKs) they also inhibit MAPK9, i.e. c-Jun-N-terminal kinase 2...
- Jezierski M, Sturm A, Scarborough M, Sohrabji F. NGF stimulation increases JNK2 phosphorylation and reduces caspase-3 activity in the olfactory bulb of estrogen-replaced animals. Endocrinology. 2001;142:2401 pubmed..In view of the disparate roles assigned to JNK, this latter finding suggests that estrogen pretreatment may preferentially direct neurotrophin-dependent JNK activation toward regeneration and plasticity rather than cell death. ..
- Park H, Kim B, Kim S, Choi K. Role of MAP kinases and their cross-talk in TGF-beta1-induced apoptosis in FaO rat hepatoma cell line. Hepatology. 2002;35:1360-71 pubmed..In conclusion, we propose that the balance and integration of MAP kinase signaling may regulate commitment to TGF-beta1-induced apoptosis modulating the release of cytochrome c from mitochondria. ..
- Chen D, Wei X, Guan J, Yuan J, Peng Y, Song L, et al. Inhibition of c-Jun N-terminal kinase prevents blood-brain barrier disruption and normalizes the expression of tight junction proteins clautin-5 and ZO-1 in a rat model of subarachnoid hemorrhage. Acta Neurochir (Wien). 2012;154:1469-76; discussion 1476 pubmed publisher..Our data demonstrate that the JNK signaling plays an important role in the regulation of tight junction proteins and BBB integrity, and thus represents a promising target against brain injuries after SAH. ..
- Syed I, Kyathanahalli C, Jayaram B, Govind S, Rhodes C, Kowluru R, et al. Increased phagocyte-like NADPH oxidase and ROS generation in type 2 diabetic ZDF rat and human islets: role of Rac1-JNK1/2 signaling pathway in mitochondrial dysregulation in the diabetic islet. Diabetes. 2011;60:2843-52 pubmed publisher..We provide the first in vitro and in vivo evidence in support of an accelerated Rac1-Nox-ROS-JNK1/2 signaling pathway in the islet ?-cell leading to the onset of mitochondrial dysregulation in diabetes. ..
- Zhang P, Hogan E, Bhat N. Activation of JNK/SAPK in primary glial cultures: II. Differential activation of kinase isoforms corresponds to their differential expression. Neurochem Res. 1998;23:219-25 pubmed..Immunoblot and immunocytochemical analyses using isoform-specific antibodies showed a differential expression of the two isoforms in different glial cells thereby accounting for their observed differential activation. ..
- Fan Y, Shimizu T, Yamada T, Nanashima N, Akita M, Asano J, et al. Development of glutathione S-transferase-P-negative foci accompanying nuclear factor-erythroid 2-related factor 2 expression during early stage of rat hepatocarcinogenesis. Cancer Sci. 2008;99:497-501 pubmed..These results showed development of GST-P-negative foci during the early stage of hepatocarcinogenesis and suggested that Nrf2 is not responsible for GST-P expression in rat hepatic preneoplastic foci. ..
- Kyriakis J, Banerjee P, Nikolakaki E, Dai T, Rubie E, Ahmad M, et al. The stress-activated protein kinase subfamily of c-Jun kinases. Nature. 1994;369:156-60 pubmed..9). SAPKs therefore define a new TNF-alpha and stress-activated signalling pathway, possibly initiated by sphingomyelin-based second messengers, which regulates the activity of c-Jun. ..
- Gupta S, Barrett T, Whitmarsh A, Cavanagh J, Sluss H, Derijard B, et al. Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J. 1996;15:2760-70 pubmed..Individual members of the JNK group may therefore selectively target specific transcription factors in vivo. ..
- Chaudhary L, Avioli L. Activation of c-Jun NH2-terminal kinases by interleukin-1 beta in normal human osteoblastic and rat UMR-106 cells. J Cell Biochem. 1998;69:87-93 pubmed..Results have clearly demonstrated that IL-1 beta preferentially activates JNK pathway whereas FGF-2 activates ERK pathway in normal human and rat UMR-106 osteoblastic cells. ..
- Wang Y, Luo W, Reiser G. Proteinase-activated receptor-1 and -2 induce the release of chemokine GRO/CINC-1 from rat astrocytes via differential activation of JNK isoforms, evoking multiple protective pathways in brain. Biochem J. 2007;401:65-78 pubmed..This provides new functional insights into PAR/JNK signalling and the protective actions of PARs in brain. ..
- Eminel S, Klettner A, Roemer L, Herdegen T, Waetzig V. JNK2 translocates to the mitochondria and mediates cytochrome c release in PC12 cells in response to 6-hydroxydopamine. J Biol Chem. 2004;279:55385-92 pubmed..Our data provide novel functional insights into the pathological role of individual JNK isoforms, the signalosome at the mitochondria, and the mode of JNK-induced release of cytochrome c. ..
- Carboni L, Carletti R, Tacconi S, Corti C, Ferraguti F. Differential expression of SAPK isoforms in the rat brain. An in situ hybridisation study in the adult rat brain and during post-natal development. Brain Res Mol Brain Res. 1998;60:57-68 pubmed..As a first step to elucidate the role of MAPK pathways in neuronal signalling, we studied the distribution of SAPK alpha/JNK2, SAPK beta/JNK3, and SAPK gamma/JNK1, three isoforms of SAPK/JNK, a stress-activated MAPK subfamily...
- Zhu X, Raina A, Rottkamp C, Aliev G, Perry G, Boux H, et al. Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. J Neurochem. 2001;76:435-41 pubmed..In this regard, we suspect that c-Jun N-terminal kinase/Stress activated protein kinase (JNK/SAPK), a major cellular stress response protein induced by oxidative stress, plays an important role in Alzheimer ..
- Yoshitane H, Honma S, Imamura K, Nakajima H, Nishide S, Ono D, et al. JNK regulates the photic response of the mammalian circadian clock. EMBO Rep. 2012;13:455-61 pubmed publisher..Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light. ..
- Liu C, Lo J, Kuo C, Chu C, Chen L, Tsai F, et al. Akt mediates 17beta-estradiol and/or estrogen receptor-alpha inhibition of LPS-induced tumor necresis factor-alpha expression and myocardial cell apoptosis by suppressing the JNK1/2-NFkappaB pathway. J Cell Mol Med. 2009;13:3655-67 pubmed publisher..These findings suggest that E(2), BSA-E(2) and ERalpha expression exert their cardioprotective effects by inhibiting JNK1/2-mediated LPS-induced TNF-alpha expression and cardiomyocyte apoptosis through activation of Akt. ..
- Zhao E, Amir M, Lin Y, Czaja M. Stathmin mediates hepatocyte resistance to death from oxidative stress by down regulating JNK. PLoS ONE. 2014;9:e109750 pubmed publisher..These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth. ..
- Jiang Q, Gu Z, Zhang G. Activation, involvement and nuclear translocation of c-Jun N-terminal protein kinase 1 and 2 in glutamate-induced apoptosis in cultured rat cortical neurons. Brain Res. 2002;956:194-201 pubmed
- Sui H, Cai G, Pan S, Deng W, Wang Y, Chen Z, et al. miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. Mol Cancer Ther. 2014;13:3137-51 pubmed publisher..Restoration of miR200c expression in MDR colorectal cancer may serve as a promising therapeutic approach in MDR-induced metastasis. ..
- Papadakis E, Finegan K, Wang X, Robinson A, Guo C, Kayahara M, et al. The regulation of Bax by c-Jun N-terminal protein kinase (JNK) is a prerequisite to the mitochondrial-induced apoptotic pathway. FEBS Lett. 2006;580:1320-6 pubmed..The absence of apoptotic death correlates with a specific defect in activation of Bax. We conclude that JNK-dependent regulation of Bax is essential to mediate the apoptotic release of cytochrome c regardless of Bid and Bim activation. ..
- Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner E. Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech Dev. 1999;89:115-24 pubmed..These results assign both pro- and anti-apoptotic functions for JNK1 and JNK2 in the development of the fetal brain. ..
- Zhang L, Xing D, Liu L, Gao X, Chen M. TNFalpha induces apoptosis through JNK/Bax-dependent pathway in differentiated, but not naïve PC12 cells. Cell Cycle. 2007;6:1479-86 pubmed..The experimental data strongly demonstrated that TNFalpha induced apoptosis through JNK/Bax-dependent pathway in differentiated, but not naïve PC12 cells. ..
- Oh Y, Kim J, Kang C. Effects of ethanol on insulin-like growth factor-I system in primary cultured rat hepatocytes: implications of JNK1/2 and alcoholdehydrogenase. World J Gastroenterol. 2008;14:4324-31 pubmed..Furthermore, alcohol dehydrogenase is involved in the relationship between ethanol-induced inactivation of p-JNK1/2 and the changes of the IGF-I system and cell viability. ..
- Posser T, de Aguiar C, Garcez R, Rossi F, Oliveira C, Trentin A, et al. Exposure of C6 glioma cells to Pb(II) increases the phosphorylation of p38(MAPK) and JNK1/2 but not of ERK1/2. Arch Toxicol. 2007;81:407-14 pubmed..Therefore, depending on a long incubation period, a significant concomitant activation of p38(MAPK) and JNK1/2 by Pb(II) took place in parallel with the impairment of C6 glioma cells viability. ..
- Johnson G, Nakamura K. The c-jun kinase/stress-activated pathway: regulation, function and role in human disease. Biochim Biophys Acta. 2007;1773:1341-8 pubmed..In this review, we present our current understanding of JNK regulation and their involvement in homeostasis and dysregulation in human disease. ..
- Hong I, Park S, Goo M, Lee H, Park J, Ki M, et al. JNK1 and JNK2 regulate ?-SMA in hepatic stellate cells during CCl4 -induced fibrosis in the rat liver. Pathol Int. 2013;63:483-91 pubmed publisher..We suggest that JNKs are responsible for ?-SMA regulation, and especially JNK1 has a major role in up-regulation of ?-SMA expression in HSCs under stress condition induced by TGF-? during liver fibrosis. ..
- Zhang Q, Pei D, Guan Q, Sun Y, Liu X, Zhang G. Crosstalk between PSD-95 and JIP1-mediated signaling modules: the mechanism of MLK3 activation in cerebral ischemia. Biochemistry. 2007;46:4006-16 pubmed..Thus, specific blockade of PSD-95-MLK3 coupling may reduce the extent of ischemia-reperfusion-induced neuronal cell death. ..
- Papachristou D, Pirttiniemi P, Kantomaa T, Papavassiliou A, Basdra E. JNK/ERK-AP-1/Runx2 induction "paves the way" to cartilage load-ignited chondroblastic differentiation. Histochem Cell Biol. 2005;124:215-23 pubmed
- Davila D, Torres Aleman I. Neuronal death by oxidative stress involves activation of FOXO3 through a two-arm pathway that activates stress kinases and attenuates insulin-like growth factor I signaling. Mol Biol Cell. 2008;19:2014-25 pubmed publisher..In view of previous observations linking attenuation of IGF-I signaling to other causes of neuronal death, these findings suggest that blockade of trophic input is a common step in neuronal death. ..
- Hreniuk D, Garay M, Gaarde W, Monia B, McKay R, Cioffi C. Inhibition of c-Jun N-terminal kinase 1, but not c-Jun N-terminal kinase 2, suppresses apoptosis induced by ischemia/reoxygenation in rat cardiac myocytes. Mol Pharmacol. 2001;59:867-74 pubmed..These findings demonstrate that the JNK1 isoform plays a preferential role in apoptosis induced by ischemia/reoxygenation as well as diverse JNK-activating cellular stresses. ..
- Fogarty M, Downer E, Campbell V. A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, in the beta-amyloid-mediated stabilization of protein p53 and induction of the apoptotic cascade in cultured cortical neurons. Biochem J. 2003;371:789-98 pubmed..These results demonstrate a significant role for JNK1 in A beta-mediated induction of the apoptotic cascade in cultured cortical neurons. ..
- Katayama I, Hotokezaka Y, Matsuyama T, Sumi T, Nakamura T. Ionizing radiation induces macrophage foam cell formation and aggregation through JNK-dependent activation of CD36 scavenger receptors. Int J Radiat Oncol Biol Phys. 2008;70:835-46 pubmed publisher..Taken together, these results suggest that IR-induced foam cell formation is mediated by c-Jun N-terminal kinase-dependent CD36 activation. ..
- Tanabe K, Nishimura K, Dohi S, Kozawa O. Mechanisms of interleukin-1beta-induced GDNF release from rat glioma cells. Brain Res. 2009;1274:11-20 pubmed publisher..protein (MAP) kinase, p44/p42 MAP kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and signal transducer and activator of transcription (STAT) 3...
- Lal H, Verma S, Golden H, Foster D, Smith M, Dostal D. Stretch-induced regulation of angiotensinogen gene expression in cardiac myocytes and fibroblasts: opposing roles of JNK1/2 and p38alpha MAP kinases. J Mol Cell Cardiol. 2008;45:770-8 pubmed publisher..This suggests that a balance in JNK1/2 and p38alpha activation determines the level of Ao gene expression in myocardial cells. ..
- Rardin M, Wiley S, Murphy A, Pagliarini D, Dixon J. Dual specificity phosphatases 18 and 21 target to opposing sides of the mitochondrial inner membrane. J Biol Chem. 2008;283:15440-50 pubmed publisher..This work rigorously demonstrates the unique location of two highly similar DSPs on opposing sides of the mitochondrial inner membrane...
- Guan Z, Buckman S, Springer L, Morrison A. Both p38alpha(MAPK) and JNK/SAPK pathways are important for induction of nitric-oxide synthase by interleukin-1beta in rat glomerular mesangial cells. J Biol Chem. 1999;274:36200-6 pubmed..These events are preceded by activation of the c-Jun NH(2)-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38(MAPK)...
- Heidbreder M, Naumann A, Tempel K, Dominiak P, Dendorfer A. Remote vs. ischaemic preconditioning: the differential role of mitogen-activated protein kinase pathways. Cardiovasc Res. 2008;78:108-15 pubmed..All investigated MAPK pathways appear to be involved in RPC-induced cardioprotection; however, they do not contribute to the alterations that define the preconditioned state of the myocardium prior to the infarction. ..
- Lin C, Hsiao W, Huang C, Kao C, Hsu G. Heme oxygenase-1 induction by the ROS-JNK pathway plays a role in aluminum-induced anemia. J Inorg Biochem. 2013;128:221-8 pubmed publisher..Thus, Al enhances HO-1 expression through the ROS-JNK pathway, which may enhance HO activity and accelerate degradation of heme, leading to hypochromic anemia. ..
- Pan Y, Tseng W, Chang P, Chen H. Phosphorylation of moesin by Jun N-terminal kinase is important for podosome rosette formation in Src-transformed fibroblasts. J Cell Sci. 2013;126:5670-80 pubmed publisher..Taken together, our results unveil a novel role of JNK in podosome rosette formation through the phosphorylation of moesin. ..
- Downer E, Fogarty M, Campbell V. Tetrahydrocannabinol-induced neurotoxicity depends on CB1 receptor-mediated c-Jun N-terminal kinase activation in cultured cortical neurons. Br J Pharmacol. 2003;140:547-57 pubmed..The data demonstrate that the activation of both JNK1 and JNK2 isoforms is central to the THC-induced activation of the apoptotic pathway in cortical neurons. ..
- Samak G, Suzuki T, Bhargava A, Rao R. c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2010;299:G572-84 pubmed publisher..These results reveal the role of JNK2 in the mechanism of osmotic stress-induced TJ disruption in the intestinal epithelium. ..