PMID- 10521462 OWN - NLM STAT- MEDLINE DCOM- 19991123 LR - 20220309 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 43 DP - 1999 Oct 22 TI - TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton. PG - 30729-37 AB - Germinal center kinases (GCKs) compose a subgroup of the Ste20 family of kinases. Here we describe the cloning and characterization of a novel GCK family kinase, Traf2- and Nck-interacting kinase (TNIK) that interacts with both Traf2 and Nck. TNIK encodes a polypeptide of 1360 amino acids with eight spliced isoforms. It has 90% amino acid identity to the Nck-interacting kinase in both the N-terminal kinase domain and the C-terminal germinal center kinase homology region. The homology drops to 53% in the intermediate region. TNIK specifically activates the c-Jun N-terminal kinase pathway when transfected into Phoenix-A cells (derivatives of 293 cells), similar to many GCKs. However, in contrast to other GCKs, this activation is mediated solely by the GCK homology region of TNIK. In addition, in Phoenix-A, NIH-3T3, and Hela cells, overexpression of wild type TNIK, but not the kinase mutant form of TNIK, results in the disruption of F-actin structure and the inhibition of cell spreading. Furthermore, TNIK can phosphorylate Gelsolin in vitro. This is the first time that a GCK family kinase is shown to be potentially involved in the regulation of cytoskeleton. FAU - Fu, C A AU - Fu CA AD - Rigel, Inc., South San Francisco, California 94080, USA. FAU - Shen, M AU - Shen M FAU - Huang, B C AU - Huang BC FAU - Lasaga, J AU - Lasaga J FAU - Payan, D G AU - Payan DG FAU - Luo, Y AU - Luo Y LA - eng SI - GENBANK/AF172264 SI - GENBANK/AF172265 SI - GENBANK/AF172266 SI - GENBANK/AF172267 SI - GENBANK/AF172268 SI - GENBANK/AF172269 SI - GENBANK/AF172270 SI - GENBANK/AF172271 PT - Journal Article PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Germinal Center Kinases) RN - 0 (Nck protein) RN - 0 (Oncogene Proteins) RN - 0 (Proteins) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Recombinant Proteins) RN - 0 (TNF Receptor-Associated Factor 2) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (TNIK protein, human) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - 3T3 Cells MH - Adaptor Proteins, Signal Transducing MH - Alternative Splicing MH - Amino Acid Sequence MH - Animals MH - Brain/enzymology MH - Cell Line MH - Cloning, Molecular MH - Cytoskeleton/*physiology MH - Gene Library MH - Germinal Center/*physiology MH - Germinal Center Kinases MH - HeLa Cells MH - Humans MH - JNK Mitogen-Activated Protein Kinases MH - Mice MH - Mitogen-Activated Protein Kinases/*metabolism MH - Molecular Sequence Data MH - Oncogene Proteins/metabolism MH - Protein Serine-Threonine Kinases/metabolism MH - Proteins/metabolism MH - Receptors, Tumor Necrosis Factor/metabolism MH - Recombinant Proteins/chemistry/metabolism MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - TNF Receptor-Associated Factor 2 MH - Transfection MH - src Homology Domains EDAT- 1999/10/16 00:00 MHDA- 1999/10/16 00:01 CRDT- 1999/10/16 00:00 PHST- 1999/10/16 00:00 [pubmed] PHST- 1999/10/16 00:01 [medline] PHST- 1999/10/16 00:00 [entrez] AID - 10.1074/jbc.274.43.30729 [doi] AID - S0021-9258(19)51742-2 [pii] PST - ppublish SO - J Biol Chem. 1999 Oct 22;274(43):30729-37. doi: 10.1074/jbc.274.43.30729.