HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yao, Z. Articles by Tan, T.-H. Search for Related Content PubMed PubMed Citation Articles by Yao, Z. Articles by Tan, T.-H.

J Biol Chem, Vol. 274, Issue 4, 2118-2125, January 22, 1999

A Novel Human STE20-related Protein Kinase, HGK, That Specifically Activates the c-Jun N-terminal Kinase Signaling Pathway

Zhengbin Yao, Guisheng Zhou^¶, Xuhong Sunny Wang, Amy Brown^¶, Katrina Diener, Hong Gan^¶, and Tse-Hua Tan^¶

From  Amgen, Inc., Boulder, Colorado 80301 and the ^¶ Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030

The yeast serine/threonine kinase STE20 activates a signaling cascade that includes STE11 (mitogen-activated protein kinase kinase kinase), STE7 (mitogen-activated protein kinase kinase), and FUS3/KSS1 (mitogen-activated protein kinase) in response to signals from both Cdc42 and the heterotrimeric G proteins associated with transmembrane pheromone receptors. Using degenerate polymerase chain reaction, we have isolated a human cDNA encoding a protein kinase homologous to STE20. This protein kinase, designated HPK/GCK-like kinase (HGK), has nucleotide sequences that encode an open reading frame of 1165 amino acids with 11 kinase subdomains. HGK was a serine/threonine protein kinase that specifically activated the c-Jun N-terminal kinase (JNK) signaling pathway when transfected into 293T cells, but it did not stimulate either the extracellular signal-regulated kinase or p38 kinase pathway. HGK also increased AP-1-mediated transcriptional activity in vivo. HGK-induced JNK activation was inhibited by the dominant-negative MKK4 and MKK7 mutants. The dominant-negative mutant of TAK1, but not MEKK1 or MAPK upstream kinase (MUK), strongly inhibited HGK-induced JNK activation. TNF- activated HGK in 293T cells, as well as the dominant-negative HGK mutants, inhibited TNF--induced JNK activation. These results indicate that HGK, a novel activator of the JNK pathway, may function through TAK1, and that the HGK  TAK1  MKK4, MKK7  JNK kinase cascade may mediate the TNF- signaling pathway.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				G. J. Tesz, A. Guilherme, K. V. P. Guntur, A. C. Hubbard, X. Tang, A. Chawla, and M. P. Czech Tumor Necrosis Factor {alpha} (TNF{alpha}) Stimulates Map4k4 Expression through TNF{alpha} Receptor 1 Signaling to c-Jun and Activating Transcription Factor 2 J. Biol. Chem., July 6, 2007; 282(27): 19302 - 19312. [Abstract] [Full Text] [PDF]

				K. Bouzakri and J. R. Zierath MAP4K4 Gene Silencing in Human Skeletal Muscle Prevents Tumor Necrosis Factor-{alpha}-induced Insulin Resistance J. Biol. Chem., March 16, 2007; 282(11): 7783 - 7789. [Abstract] [Full Text] [PDF]

				M. Xie, D. Zhang, J. R. B. Dyck, Y. Li, H. Zhang, M. Morishima, D. L. Mann, G. E. Taffet, A. Baldini, D. S. Khoury, et al. A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway PNAS, November 14, 2006; 103(46): 17378 - 17383. [Abstract] [Full Text] [PDF]

				J. Mao, K. L. Ligon, E. Y. Rakhlin, S. P. Thayer, R. T. Bronson, D. Rowitch, and A. P. McMahon A novel somatic mouse model to survey tumorigenic potential applied to the hedgehog pathway. Cancer Res., October 15, 2006; 66(20): 10171 - 10178. [Abstract] [Full Text] [PDF]

				C. S. Collins, J. Hong, L. Sapinoso, Y. Zhou, Z. Liu, K. Micklash, P. G. Schultz, and G. M. Hampton A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. PNAS, March 7, 2006; 103(10): 3775 - 3780. [Abstract] [Full Text] [PDF]

				X. Tang, A. Guilherme, A. Chakladar, A. M. Powelka, S. Konda, J. V. Virbasius, S. M. C. Nicoloro, J. Straubhaar, and M. P. Czech An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPAR{gamma}, adipogenesis, and insulin-responsive hexose transport PNAS, February 14, 2006; 103(7): 2087 - 2092. [Abstract] [Full Text] [PDF]

				S. E. Kendall, C. Battelli, S. Irwin, J. G. Mitchell, C. A. Glackin, and J. M. Verdi NRAGE Mediates p38 Activation and Neural Progenitor Apoptosis via the Bone Morphogenetic Protein Signaling Cascade Mol. Cell. Biol., September 1, 2005; 25(17): 7711 - 7724. [Abstract] [Full Text] [PDF]

				C. Miled, M. Pontoglio, S. Garbay, M. Yaniv, and J. B. Weitzman A Genomic Map of p53 Binding Sites Identifies Novel p53 Targets Involved in an Apoptotic Network Cancer Res., June 15, 2005; 65(12): 5096 - 5104. [Abstract] [Full Text] [PDF]

				Y. Hu, C. Leo, S. Yu, B. C. B. Huang, H. Wang, M. Shen, Y. Luo, S. Daniel-Issakani, D. G. Payan, and X. Xu Identification and Functional Characterization of a Novel Human Misshapen/Nck Interacting Kinase-related Kinase, hMINK{beta} J. Biol. Chem., December 24, 2004; 279(52): 54387 - 54397. [Abstract] [Full Text] [PDF]

				K. Taira, M. Umikawa, K. Takei, B.-E. Myagmar, M. Shinzato, N. Machida, H. Uezato, S. Nonaka, and K.-i. Kariya The Traf2- and Nck-interacting Kinase as a Putative Effector of Rap2 to Regulate Actin Cytoskeleton J. Biol. Chem., November 19, 2004; 279(47): 49488 - 49496. [Abstract] [Full Text] [PDF]

				N. Machida, M. Umikawa, K. Takei, N. Sakima, B.-E. Myagmar, K. Taira, H. Uezato, Y. Ogawa, and K.-i. Kariya Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 as a Putative Effector of Rap2 to Activate the c-Jun N-terminal Kinase J. Biol. Chem., April 16, 2004; 279(16): 15711 - 15714. [Abstract] [Full Text] [PDF]

				W. Chen, M. Yazicioglu, and M. H. Cobb Characterization of OSR1, a Member of the Mammalian Ste20p/Germinal Center Kinase Subfamily J. Biol. Chem., March 19, 2004; 279(12): 11129 - 11136. [Abstract] [Full Text] [PDF]

				K. Nishigaki, D. Thompson, T. Yugawa, K. Rulli, C. Hanson, J. Cmarik, J. S. Gutkind, H. Teramoto, and S. Ruscetti Identification and Characterization of a Novel Ste20/Germinal Center Kinase-related Kinase, Polyploidy-associated Protein Kinase J. Biol. Chem., April 4, 2003; 278(15): 13520 - 13530. [Abstract] [Full Text] [PDF]

				J. H. Wright, X. Wang, G. Manning, B. J. LaMere, P. Le, S. Zhu, D. Khatry, P. M. Flanagan, S. D. Buckley, D. B. Whyte, et al. The STE20 Kinase HGK Is Broadly Expressed in Human Tumor Cells and Can Modulate Cellular Transformation, Invasion, and Adhesion Mol. Cell. Biol., March 15, 2003; 23(6): 2068 - 2082. [Abstract] [Full Text] [PDF]

				M. M. Mc Gee, G. Campiani, A. Ramunno, V. Nacci, M. Lawler, D. C. Williams, and D. M. Zisterer Activation of the c-Jun N-terminal Kinase (JNK) Signaling Pathway Is Essential during PBOX-6-induced Apoptosis in Chronic Myelogenous Leukemia (CML) Cells J. Biol. Chem., May 17, 2002; 277(21): 18383 - 18389. [Abstract] [Full Text] [PDF]

				G. Zhou, K. A. Mihindukulasuriya, R. A. MacCorkle-Chosnek, A. Van Hooser, M. C.-T. Hu, B. R. Brinkley, and T.-H. Tan Protein Phosphatase 4 Is Involved in Tumor Necrosis Factor-alpha -induced Activation of c-Jun N-terminal Kinase J. Biol. Chem., February 15, 2002; 277(8): 6391 - 6398. [Abstract] [Full Text] [PDF]

				C. A. Bradham, E. Hatano, and D. A. Brenner Dominant-negative TAK1 induces c-Myc and G0 exit in liver Am J Physiol Gastrointest Liver Physiol, November 1, 2001; 281(5): G1279 - G1289. [Abstract] [Full Text] [PDF]

				G. Pearson, F. Robinson, T. Beers Gibson, B.-e Xu, M. Karandikar, K. Berman, and M. H. Cobb Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions Endocr. Rev., April 1, 2001; 22(2): 153 - 183. [Abstract] [Full Text]

				J. M. Kyriakis and J. Avruch Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation Physiol Rev, April 1, 2001; 81(2): 807 - 869. [Abstract] [Full Text] [PDF]

				K. Kishimoto, K. Matsumoto, and J. Ninomiya-Tsuji TAK1 Mitogen-activated Protein Kinase Kinase Kinase Is Activated by Autophosphorylation within Its Activation Loop J. Biol. Chem., March 15, 2000; 275(10): 7359 - 7364. [Abstract] [Full Text] [PDF]

				T. M. Moore, R. Garg, C. Johnson, M. J. Coptcoat, A. J. Ridley, and J. D. H. Morris PSK, a Novel STE20-like Kinase Derived from Prostatic Carcinoma That Activates the c-Jun N-terminal Kinase Mitogen-activated Protein Kinase Pathway and Regulates Actin Cytoskeletal Organization J. Biol. Chem., February 11, 2000; 275(6): 4311 - 4322. [Abstract] [Full Text] [PDF]

				T.-H. Zhou, K. Ling, J. Guo, H. Zhou, Y.-L. Wu, Q. Jing, L. Ma, and G. Pei Identification of a Human Brain-specific Isoform of Mammalian STE20-like Kinase 3 That Is Regulated by cAMP-dependent Protein Kinase J. Biol. Chem., January 28, 2000; 275(4): 2513 - 2519. [Abstract] [Full Text] [PDF]

				J Behrens Cross-regulation of the Wnt signalling pathway: a role of MAP kinases J. Cell Sci., January 3, 2000; 113(6): 911 - 919. [Abstract] [PDF]

				S. Dorion, J. Berube, J. Huot, and J. Landry A Short Lived Protein Involved in the Heat Shock Sensing Mechanism Responsible for Stress-activated Protein Kinase 2 (SAPK2/p38) Activation J. Biol. Chem., December 31, 1999; 274(53): 37591 - 37597. [Abstract] [Full Text] [PDF]

				D. Ensenat, Z. Yao, X. S. Wang, R. Kori, G. Zhou, S. C. Lee, and T.-H. Tan A Novel Src Homology 3 Domain-containing Adaptor Protein, HIP-55, That Interacts with Hematopoietic Progenitor Kinase 1 J. Biol. Chem., November 26, 1999; 274(48): 33945 - 33950. [Abstract] [Full Text] [PDF]

				C. A. Fu, M. Shen, B. C. B. Huang, J. Lasaga, D. G. Payan, and Y. Luo TNIK, a Novel Member of the Germinal Center Kinase Family That Activates the c-Jun N-terminal Kinase Pathway and Regulates the Cytoskeleton J. Biol. Chem., October 22, 1999; 274(43): 30729 - 30737. [Abstract] [Full Text] [PDF]

				C.-S. Shi, A. Leonardi, J. Kyriakis, U. Siebenlist, and J. H. Kehrl TNF-Mediated Activation of the Stress-Activated Protein Kinase Pathway: TNF Receptor-Associated Factor 2 Recruits and Activates Germinal Center Kinase Related J. Immunol., September 15, 1999; 163(6): 3279 - 3285. [Abstract] [Full Text] [PDF]

				G. Zhou, S. C. Lee, Z. Yao, and T.-H. Tan Hematopoietic Progenitor Kinase 1 Is a Component of Transforming Growth Factor beta -induced c-Jun N-terminal Kinase Signaling Cascade J. Biol. Chem., May 7, 1999; 274(19): 13133 - 13138. [Abstract] [Full Text] [PDF]

				K. Nakano, J. Yamauchi, K. Nakagawa, H. Itoh, and N. Kitamura NESK, a Member of the Germinal Center Kinase Family That Activates the c-Jun N-terminal Kinase Pathway and Is Expressed during the Late Stages of Embryogenesis J. Biol. Chem., June 30, 2000; 275(27): 20533 - 20539. [Abstract] [Full Text] [PDF]

				Y. Ito, P. Pandey, P. Sathyanarayana, P. Ling, A. Rana, R. Weichselbaum, T.-H. Tan, D. Kufe, and S. Kharbanda Interaction of Hematopoietic Progenitor Kinase 1 and c-Abl Tyrosine Kinase in Response to Genotoxic Stress J. Biol. Chem., May 18, 2001; 276(21): 18130 - 18138. [Abstract] [Full Text] [PDF]

				D. Krause, A. Lyons, C. Fennelly, and R. O'Connor Transient Activation of Jun N-terminal Kinases and Protection from Apoptosis by the Insulin-like Growth Factor I Receptor Can Be Suppressed by Dicumarol J. Biol. Chem., May 25, 2001; 276(22): 19244 - 19252. [Abstract] [Full Text] [PDF]

				Z. Qian, C. Lin, R. Espinosa, M. LeBeau, and M. R. Rosner Cloning and Characterization of MST4, a Novel Ste20-like Kinase J. Biol. Chem., June 15, 2001; 276(25): 22439 - 22445. [Abstract] [Full Text] [PDF]

				M. Izumi, Y. Fujio, K. Kunisada, S. Negoro, E. Tone, M. Funamoto, T. Osugi, Y. Oshima, Y. Nakaoka, T. Kishimoto, et al. Bone Morphogenetic Protein-2 Inhibits Serum Deprivation-induced Apoptosis of Neonatal Cardiac Myocytes through Activation of the Smad1 Pathway J. Biol. Chem., August 10, 2001; 276(33): 31133 - 31141. [Abstract] [Full Text] [PDF]

				P. Ling, C. F. Meyer, L. P. Redmond, J.-W. Shui, B. Davis, R. R. Rich, M. C.-T. Hu, R. L. Wange, and T.-H. Tan Involvement of Hematopoietic Progenitor Kinase 1 in T Cell Receptor Signaling J. Biol. Chem., May 25, 2001; 276(22): 18908 - 18914. [Abstract] [Full Text] [PDF]

				N. Kimura, R. Matsuo, H. Shibuya, K. Nakashima, and T. Taga BMP2-induced Apoptosis Is Mediated by Activation of the TAK1-p38 Kinase Pathway That Is Negatively Regulated by Smad6 J. Biol. Chem., June 2, 2000; 275(23): 17647 - 17652. [Abstract] [Full Text] [PDF]