Genomes and Genes
map kinase kinase 7
Summary: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to CYTOKINES.
- Bruna A, Nicolas M, Munoz A, Kyriakis J, Caelles C. Glucocorticoid receptor-JNK interaction mediates inhibition of the JNK pathway by glucocorticoids. EMBO J. 2003;22:6035-44 pubmed..In this regard, chromatin immunoprecipitation assays show that GC-induced GR-JNK association correlates with an increase in the loading of inactive JNK on the AP-1-bound response elements of the c-jun gene. ..
- Parkinson D, Bhaskaran A, Droggiti A, Dickinson S, D Antonio M, Mirsky R, et al. Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death. J Cell Biol. 2004;164:385-94 pubmed..Krox-20 also up-regulates the scaffold protein JNK-interacting protein 1 (JIP-1). We propose this as a possible component of the mechanism by which Krox-20 regulates JNK activity during Schwann cell development. ..
- Cui J, Wang Q, Wang J, Lv M, Zhu N, Li Y, et al. Basal c-Jun NH2-terminal protein kinase activity is essential for survival and proliferation of T-cell acute lymphoblastic leukemia cells. Mol Cancer Ther. 2009;8:3214-22 pubmed publisher..Thus, our work suggests that there might be novel mechanism(s) other than hyperactivation underlying the protumorigenic role of JNK activity. ..
- Svensson C, Inoue T, Hammaker D, Fukushima A, Papa S, Franzoso G, et al. Gadd45beta deficiency in rheumatoid arthritis: enhanced synovitis through JNK signaling. Arthritis Rheum. 2009;60:3229-40 pubmed publisher..This process can be mitigated by enhancing Gadd45beta expression or by inhibiting the activity of JNK or its upstream regulator, MKK-7. ..
- Yasuda J, Whitmarsh A, Cavanagh J, Sharma M, Davis R. The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol. 1999;19:7245-54 pubmed..JIP) group of scaffold proteins selectively mediates signaling by the mixed-lineage kinase (MLK)-->MAP kinase kinase 7 (MKK7)-->JNK pathway...
- Whitmarsh A, Cavanagh J, Tournier C, Yasuda J, Davis R. A mammalian scaffold complex that selectively mediates MAP kinase activation. Science. 1998;281:1671-4 pubmed..This scaffold protein selectively enhanced JNK activation by the MLK signaling pathway. These data establish that a mammalian scaffold protein can mediate activation of a MAP kinase signaling pathway. ..
- Holland P, Suzanne M, Campbell J, Noselli S, Cooper J. MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous. J Biol Chem. 1997;272:24994-8 pubmed..MKK7 directly phosphorylates and activates JNK/SAPK. Thus, MKK7 is a homolog of hep and functions in a conserved signaling pathway involving JNK/SAPK and the GTPase Rac1. ..
- Parkinson D, Bhaskaran A, Arthur Farraj P, Noon L, Woodhoo A, Lloyd A, et al. c-Jun is a negative regulator of myelination. J Cell Biol. 2008;181:625-37 pubmed publisher..Negative regulation of myelination is likely to have significant implications for three areas of Schwann cell biology: the molecular analysis of plasticity, demyelinating pathologies, and the response of peripheral nerves to injury...
- Zhang X, Dai Y, Xiong Y, DeFraia C, Li J, Dong X, et al. Overexpression of Arabidopsis MAP kinase kinase 7 leads to activation of plant basal and systemic acquired resistance. Plant J. 2007;52:1066-79 pubmed..The MAP kinase kinase 7 (MKK7) gene of Arabidopsis has previously been shown to negatively regulate polar auxin transport...
- Papa S, Zazzeroni F, Bubici C, Jayawardena S, Alvarez K, Matsuda S, et al. Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2. Nat Cell Biol. 2004;6:146-53 pubmed..These findings establish a basis for the NF-kappa B control of JNK activation and identify MKK7 as a potential target for anti-inflammatory and anti-cancer therapy. ..
- Lotan T, Lyon M, Huo D, Taxy J, Brendler C, Foster B, et al. Up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia. J Pathol. 2007;212:386-94 pubmed..The finding that higher MKK4 and MKK7 expression is associated with higher-stage prostatic tumours underscores the dynamic regulation of these proteins during prostatic tumourigenesis. ..
- Zhang Q, Tian H, Fu X, Zhang G. Delayed activation and regulation of MKK7 in hippocampal CA1 region following global cerebral ischemia in rats. Life Sci. 2003;74:37-45 pubmed
- Tu Z, Mooney S, Lee F. A subdomain of MEKK1 that is critical for binding to MKK4. Cell Signal. 2003;15:65-77 pubmed..Such mutations were also found to impair MEKK1delta-induced activation of an AP1 reporter gene. These studies point to a critical role for subdomain X in the interaction of MEKK1 with MKK4. ..
- Merritt S, Mata M, Nihalani D, Zhu C, Hu X, Holzman L. The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate. J Biol Chem. 1999;274:10195-202 pubmed..The dissimilar cellular specificity of DLK and MLK3 and the specific substrate utilization and subcellular compartmentation of DLK suggest that specific mixed lineage kinases participate in unique signal transduction events. ..
- Kishimoto H, Nakagawa K, Watanabe T, Kitagawa D, Momose H, Seo J, et al. Different properties of SEK1 and MKK7 in dual phosphorylation of stress-induced activated protein kinase SAPK/JNK in embryonic stem cells. J Biol Chem. 2003;278:16595-601 pubmed..These results indicate that the Tyr and Thr residues of SAPK/JNK are sequentially phosphorylated by SEK1 and MKK7, respectively, in the stress-stimulated ES cells. ..
- Fleming Y, Armstrong C, Morrice N, Paterson A, Goedert M, Cohen P. Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7. Biochem J. 2000;352 Pt 1:145-54 pubmed..MKK7 also phosphorylates SAPK2a/p38 at a low rate (but not SAPK3/p38 gamma or SAPK4/p38 delta), and phosphorylation occurs exclusively at the tyrosine residue, demonstrating that MKK7 is intrinsically a 'dual-specific' protein kinase. ..
- Papa S, Monti S, Vitale R, Bubici C, Jayawardena S, Alvarez K, et al. Insights into the structural basis of the GADD45beta-mediated inactivation of the JNK kinase, MKK7/JNKK2. J Biol Chem. 2007;282:19029-41 pubmed..These data provide a basis for Gadd45beta-mediated blockade of MKK7, and ultimately, TNFalpha-induced PCD. They also have important implications for treatment of widespread diseases. ..
- Yao Z, Diener K, Wang X, Zukowski M, Matsumoto G, Zhou G, et al. Activation of stress-activated protein kinases/c-Jun N-terminal protein kinases (SAPKs/JNKs) by a novel mitogen-activated protein kinase kinase. J Biol Chem. 1997;272:32378-83 pubmed..Thus, MKK7 is a new member of the MAPK kinase family that functions upstream of SAPK/JNK in the SAPK/JNK signaling pathway. ..
- Inoue T, Hammaker D, Boyle D, Firestein G. Regulation of JNK by MKK-7 in fibroblast-like synoviocytes. Arthritis Rheum. 2006;54:2127-35 pubmed..Thus, JNK function might be modulated by targeting MKK-7 to suppress cytokine-mediated FLS activation while leaving other stress responses intact. ..
- Ho D, Bardwell A, Grewal S, Iverson C, Bardwell L. Interacting JNK-docking sites in MKK7 promote binding and activation of JNK mitogen-activated protein kinases. J Biol Chem. 2006;281:13169-79 pubmed..We conclude that MKK7 contains three JNK-docking sites that interact to selectively bind JNK and contribute to JNK signal transmission and specificity. ..
- Tournier C, Dong C, Turner T, Jones S, Flavell R, Davis R. MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Genes Dev. 2001;15:1419-26 pubmed..In contrast, disruption of the Mkk7 gene alone was sufficient to prevent JNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway. ..
- Bhattacharyya A, Pathak S, Datta S, Chattopadhyay S, Basu J, Kundu M. Mitogen-activated protein kinases and nuclear factor-kappaB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages. Biochem J. 2002;368:121-9 pubmed..pylori amplifies the inflammatory response associated with gastric H. pylori infection and needs to be taken into consideration when developing therapeutics based on these signalling pathways. ..
- Takahashi S, Ebihara A, Kajiho H, Kontani K, Nishina H, Katada T. RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7. Cell Death Differ. 2011;18:645-55 pubmed publisher..However, with prolonged stress, RASSF7 protein undergoes degradation that allows cell death signaling to proceed. Our findings may account for the association of elevated RASSF7 with tumorigenesis. ..
- Tournier C, Whitmarsh A, Cavanagh J, Barrett T, Davis R. Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase. Proc Natl Acad Sci U S A. 1997;94:7337-42 pubmed..Expression of MKK7 in cultured cells causes activation of the JNK signal transduction pathway. MKK7 is therefore established to be a novel component of the JNK signal transduction pathway. ..
- Haeusgen W, Herdegen T, Waetzig V. The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7. Eur J Cell Biol. 2011;90:536-44 pubmed publisher..We also extensively describe their impact on JNK signaling, their molecular interactions resulting in the formation of context-specific signalosomes and the functional consequences of JNK deficiency. ..
- Mondal S, Mandal C, Sangwan R, Chandra S, Mandal C. Withanolide D induces apoptosis in leukemia by targeting the activation of neutral sphingomyelinase-ceramide cascade mediated by synergistic activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Mol Cancer. 2010;9:239 pubmed publisher
- Zama T, Aoki R, Kamimoto T, Inoue K, Ikeda Y, Hagiwara M. A novel dual specificity phosphatase SKRP1 interacts with the MAPK kinase MKK7 and inactivates the JNK MAPK pathway. Implication for the precise regulation of the particular MAPK pathway. J Biol Chem. 2002;277:23909-18 pubmed..Together, our findings indicate that SKRP1 interacts with its physiological substrate JNK through MKK7, thereby leading to the precise regulation of JNK activity in vivo. ..
- Chen W, White M, Cobb M. Stimulus-specific requirements for MAP3 kinases in activating the JNK pathway. J Biol Chem. 2002;277:49105-10 pubmed..On the other hand, sorbitol requires expression of four MAP3Ks to cause maximal JNK activation. Thus, we demonstrate that specific stimuli use different mechanisms to recruit distinct MAP3Ks to regulate the JNK pathway. ..
- Moriguchi T, Toyoshima F, Masuyama N, Hanafusa H, Gotoh Y, Nishida E. A novel SAPK/JNK kinase, MKK7, stimulated by TNFalpha and cellular stresses. EMBO J. 1997;16:7045-53 pubmed..Thus, MKK7 is an evolutionarily conserved MAPKK isoform which is specific for SAPK/JNK, is involved in AP-1-dependent transcription and may be a crucial mediator of TNFalpha signalling. ..
- Sasaki T, Wada T, Kishimoto H, Irie Sasaki J, Matsumoto G, Goto T, et al. The stress kinase mitogen-activated protein kinase kinase (MKK)7 is a negative regulator of antigen receptor and growth factor receptor-induced proliferation in hematopoietic cells. J Exp Med. 2001;194:757-68 pubmed..These results indicate that the MKK7-regulated stress signaling pathway can function as negative regulator of cell growth in multiple hematopoietic lineages. ..
- Tanemura S, Momose H, Shimizu N, Kitagawa D, Seo J, Yamasaki T, et al. Blockage by SP600125 of Fcepsilon receptor-induced degranulation and cytokine gene expression in mast cells is mediated through inhibition of phosphatidylinositol 3-kinase signalling pathway. J Biochem. 2009;145:345-54 pubmed publisher..Finally, we found that SP600125 specifically inhibits delta form of p110 catalytic subunit (p110delta) of PI3K. Thus, SP600125 exerts its influence on mast cell functions by inhibiting the kinase activity of PI3K, but not JNK. ..
- Papa S, Zazzeroni F, Pham C, Bubici C, Franzoso G. Linking JNK signaling to NF-kappaB: a key to survival. J Cell Sci. 2004;117:5197-208 pubmed..These recent findings might open up entirely new avenues for therapeutic intervention in chronic inflammatory diseases and certain cancers; indeed, the Gadd45beta-MKK7 interaction might be a key target for such intervention. ..
- Amin M, Mansfield P, Pakozdi A, Campbell P, Ahmed S, Martinez R, et al. Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways. Arthritis Rheum. 2007;56:1787-97 pubmed..These data support the notion that IL-18 has a unique role in inducing the secretion of angiogenic SDF-1alpha/CXCL12, MCP-1/CCL2, and VEGF in RA ST fibroblasts, via distinct signaling intermediates. ..
- Li C, Wang R, Zhang Q, Zhang G. Activated mitogen-activated protein kinase kinase 7 redistributes to the cytosol and binds to Jun N-terminal kinase-interacting protein 1 involving oxidative stress during early reperfusion in rat hippocampal CA1 region. J Neurochem. 2005;93:290-8 pubmed..The findings suggested that MKK7 activation, translocation and binding to JIP-1 were closely associated with reactive oxygen species and might play a pivotal role in the activation of the JNK signaling pathway in brain ischemic injury. ..
- Trotter L, Panton W, Hajimohamadreza I, Petalidis L, Ward R, Fleming Y, et al. Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons. Neurosci Lett. 2002;320:29-32 pubmed..These data suggest that MKK7 is responsible for activating the JNK pathway during LK-induced CGN apoptosis. ..
- Huang C, Kuo W, Chueh P, Tseng C, Chou M, Yang J. Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK. Biochem Biophys Res Commun. 2004;324:424-31 pubmed..Our findings suggest that a ZAK mediates TGF-beta-induced cardiac hypertrophic growth via a novel TGF-beta signaling pathway that can be summarized as TGF-beta>ZAK>MKK7>ANF. ..
- Barr R, Hopkins R, Watt P, Bogoyevitch M. Reverse two-hybrid screening identifies residues of JNK required for interaction with the kinase interaction motif of JNK-interacting protein-1. J Biol Chem. 2004;279:43178-89 pubmed..Therefore, the results of our unbiased reverse two-hybrid screening approach have identified residues of JNK responsible for binding JIP-1-based peptides as well as MKK4 or MKK7. ..
- Liu H, Song G, Zhou L, Hu X, Liu M, Nie J, et al. Compared analysis of LncRNA expression profiling in pdk1 gene knockout mice at two time points. Cell Physiol Biochem. 2013;32:1497-508 pubmed publisher..These data reveal differentially expressed lncRNA in mice with a myocardial-specific deletion of the pdk1 gene, which may provide new insights into the mechanism of heart failure in PDK1 knockout mice. ..
- Zhang G, He L, Wong Y, Qian P. MKK3 was involved in larval settlement of the barnacle Amphibalanus amphitrite through activating the kinase activity of p38MAPK. PLoS ONE. 2013;8:e69510 pubmed publisher..Moreover, pMKK3 levels increased after treatment with adult barnacle crude extracts, suggesting that MKK3 might mediate the stimulatory effects of adult barnacle extracts on the p38MAPK pathway. ..
- Feltrin D, Fusco L, Witte H, Moretti F, Martin K, Letzelter M, et al. Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. PLoS Biol. 2012;10:e1001439 pubmed publisher..At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation. ..
- Yamamoto K, Ichijo H, Korsmeyer S. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol. 1999;19:8469-78 pubmed..Thus, stress response kinases phosphorylate BCL-2 during cell cycle progression as a normal physiologic process to inactivate BCL-2 at G(2)/M. ..
- Chayama K, Papst P, Garrington T, Pratt J, Ishizuka T, Webb S, et al. Role of MEKK2-MEK5 in the regulation of TNF-alpha gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells. Proc Natl Acad Sci U S A. 2001;98:4599-604 pubmed..These findings suggest that JNK activation by antigen cross-linking is dependent on the MEKK2-MKK7 pathway, and cytokine production in mast cells is regulated in part by the signaling complex MEKK2-MEK5-ERK5. ..
- Kudo T, Sakamoto Y, Tamura S, Kobayashi T. Activation mechanism of c-Jun amino-terminal kinase in the course of endodermal differentiation of P19 embryonic carcinoma cells. FEBS Lett. 2003;539:29-33 pubmed
- He J, Wang F, Qi H, Li Y, Liang H. Down-regulation of alphav integrin by retroviral delivery of small interfering RNA reduces multicellular resistance of HT29. Cancer Lett. 2009;284:182-8 pubmed publisher..Since force, including adhesion, can activate alphav integrin, cell-cell contact may contribute to activation of alphav integrin, through which increasing phosphorylated p65 and decreasing phosphorylated JNK2 takes part in MCR. ..
- Popescu S, Popescu G, Bachan S, Zhang Z, Gerstein M, Snyder M, et al. MAPK target networks in Arabidopsis thaliana revealed using functional protein microarrays. Genes Dev. 2009;23:80-92 pubmed publisher..Our predicted MKK-MPK phosphorylation network constitutes a valuable resource to understand the function and specificity of MPK signaling systems. ..
- Yoshizawa T, Hammaker D, Sweeney S, Boyle D, Firestein G. Synoviocyte innate immune responses: I. Differential regulation of interferon responses and the JNK pathway by MAPK kinases. J Immunol. 2008;181:3252-8 pubmed..MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 requires both MKK4 and MKK7, with the former activating c-Jun and the latter activating both c-Jun and IRF3 through JNK-dependent mechanisms. ..
- Wang R, Zhang Q, Han D, Xu J, Lu Q, Zhang G. Inhibition of MLK3-MKK4/7-JNK1/2 pathway by Akt1 in exogenous estrogen-induced neuroprotection against transient global cerebral ischemia by a non-genomic mechanism in male rats. J Neurochem. 2006;99:1543-54 pubmed..Our data indicate that in response to estrogen, ERalpha interacts with PI3K to activate Akt1, which may inhibit the MLK3-MKK4/7-JNK1/2 pathway to protect hippocampal CA1 neurons against global cerebral ischemia in male rats. ..
- 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. ..
- Zhao Y, Herdegen T. Cerebral ischemia provokes a profound exchange of activated JNK isoforms in brain mitochondria. Mol Cell Neurosci. 2009;41:186-95 pubmed publisher..This pattern of "JNK1 goes and JNK3 comes" might be essential for the initiation of apoptosis and suggests the search for targets of compartment-specific neuroprotective strategies. ..
- Hirai S, Noda K, Moriguchi T, Nishida E, Yamashita A, Deyama T, et al. Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2. J Biol Chem. 1998;273:7406-12 pubmed..These results provide a molecular aspect to the differential regulation of the two JNK activators by a variety of cellular stimuli. ..
- Han Y, Cao X, Lin B, Lin F, Kolluri S, Stebbins J, et al. Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt. Oncogene. 2006;25:2974-86 pubmed..Together, our results demonstrate that both activation of JNK and inhibition of Akt play a role in translocation of Nur77 from the nucleus to the cytoplasm. ..
- Gandin V, Gutierrez G, Brill L, Varsano T, Feng Y, Aza Blanc P, et al. Degradation of newly synthesized polypeptides by ribosome-associated RACK1/c-Jun N-terminal kinase/eukaryotic elongation factor 1A2 complex. Mol Cell Biol. 2013;33:2510-26 pubmed publisher..These findings establish a role for a RACK1/JNK/eEF1A2 complex in the quality control of NSPs in response to stress. ..