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J Biol Chem

Title:		"A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway"
Author(s):		Yao Z; Zhou G; Wang XS; Brown A; Diener K; Gan H; Tan TH;
Address:		"Amgen, Inc., Boulder, Colorado 80301, USA"
Journal Title:		J Biol Chem
Year:		1999
Volume:		274
Issue:		4
Page Number:		2118 - 2125
DOI:		10.1074/jbc.274.4.2118
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"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-alpha activated HGK in 293T cells, as well as the dominant-negative HGK mutants, inhibited TNF-alpha-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-alpha signaling pathway"
Keywords:		"Amino Acid Sequence Calcium-Calmodulin-Dependent Protein Kinases/*metabolism Catalysis Cell Line Cloning, Molecular DNA, Complementary Enzyme Activation Humans Intracellular Signaling Peptides and Proteins JNK Mitogen-Activated Protein Kinases *MAP Kinase;"
Notes:		"MedlineYao, Z Zhou, G Wang, X S Brown, A Diener, K Gan, H Tan, T H eng R01-AI38649/AI/NIAID NIH HHS/ R01-AI42532/AI/NIAID NIH HHS/ Research Support, U.S. Gov't, P.H.S. 1999/01/16 J Biol Chem. 1999 Jan 22; 274(4):2118-25. doi: 10.1074/jbc.274.4.2118"