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The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This protein is a neuronal-specific form of c-Jun N-terminal kinases (JNKs). Through its phosphorylation and nuclear localization, this kinase plays regulatory roles in the signaling pathways during neuronal apoptosis. Beta-arrestin 2, a receptor-regulated MAP kinase scaffold protein, is found to interact with, and stimulate the phosphorylation of this kinase by MAP kinase kinase 4 (MKK4). Cyclin-dependent kinase 5 can phosphorylate, and inhibit the activity of this kinase, which may be important in preventing neuronal apoptosis. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.[3]
↑Matsuura H, Nishitoh H, Takeda K, Matsuzawa A, Amagasa T, Ito M, Yoshioka K, Ichijo H (October 2002). "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade". J. Biol. Chem. 277 (43): 40703–9. doi:10.1074/jbc.M202004200. PMID12189133.
Further reading
Freedman BD, Liu QH, Del Corno M, Collman RG (2003). "HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages". Immunol. Res. 27 (2–3): 261–76. doi:10.1385/IR:27:2-3:261. PMID12857973.
Lee C, Liu QH, Tomkowicz B, Yi Y, Freedman BD, Collman RG (2003). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways". J. Leukoc. Biol. 74 (5): 676–82. doi:10.1189/jlb.0503206. PMID12960231.
Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR (1991). "Phosphorylation of c-jun mediated by MAP kinases". Nature. 353 (6345): 670–4. doi:10.1038/353670a0. PMID1922387.
Mohit AA, Martin JH, Miller CA (1995). "p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system". Neuron. 14 (1): 67–78. doi:10.1016/0896-6273(95)90241-4. PMID7826642.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Jabado N, Pallier A, Jauliac S, Fischer A, Hivroz C (1997). "gp160 of HIV or anti-CD4 monoclonal antibody ligation of CD4 induces inhibition of JNK and ERK-2 activities in human peripheral CD4+ T lymphocytes". Eur. J. Immunol. 27 (2): 397–404. doi:10.1002/eji.1830270209. PMID9045910.
Yang DD, Kuan CY, Whitmarsh AJ, Rincón M, Zheng TS, Davis RJ, Rakic P, Flavell RA (1997). "Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene". Nature. 389 (6653): 865–70. doi:10.1038/39899. PMID9349820.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Hu MC, Qiu WR, Wang YP (1997). "JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases". Oncogene. 15 (19): 2277–87. doi:10.1038/sj.onc.1201401. PMID9393873.
Lannuzel A, Barnier JV, Hery C, Huynh VT, Guibert B, Gray F, Vincent JD, Tardieu M (1997). "Human immunodeficiency virus type 1 and its coat protein gp120 induce apoptosis and activate JNK and ERK mitogen-activated protein kinases in human neurons". Ann. Neurol. 42 (6): 847–56. doi:10.1002/ana.410420605. PMID9403476.
Xie X, Gu Y, Fox T, Coll JT, Fleming MA, Markland W, Caron PR, Wilson KP, Su MS (1998). "Crystal structure of JNK3: a kinase implicated in neuronal apoptosis". Structure. 6 (8): 983–91. doi:10.1016/S0969-2126(98)00100-2. PMID9739089.
Koyano S, Ito M, Takamatsu N, Shiba T, Yamamoto K, Yoshioka K (1999). "A novel Jun N-terminal kinase (JNK)-binding protein that enhances the activation of JNK by MEK kinase 1 and TGF-beta-activated kinase 1". FEBS Lett. 457 (3): 385–8. doi:10.1016/S0014-5793(99)01084-4. PMID10471813.
Lisnock J, Griffin P, Calaycay J, Frantz B, Parsons J, O'Keefe SJ, LoGrasso P (2000). "Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1". Biochemistry. 39 (11): 3141–8. doi:10.1021/bi992410. PMID10715136.
McDonald PH, Chow CW, Miller WE, Laporte SA, Field ME, Lin FT, Davis RJ, Lefkowitz RJ (2000). "Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3". Science. 290 (5496): 1574–7. doi:10.1126/science.290.5496.1574. PMID11090355.
2o0u: Crystal structure of human JNK3 complexed with N-{3-cyano-6-[3-(1-piperidinyl)propanoyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl}-1-naphthalenecarboxamide