ABSTRACT
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.
Subject(s)
Cytoskeleton/physiology , Germinal Center/physiology , Mitogen-Activated Protein Kinases/metabolism , 3T3 Cells , Adaptor Proteins, Signal Transducing , Alternative Splicing , Amino Acid Sequence , Animals , Brain/enzymology , Cell Line , Cloning, Molecular , Gene Library , Germinal Center Kinases , HeLa Cells , Humans , JNK Mitogen-Activated Protein Kinases , Mice , Molecular Sequence Data , Oncogene Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Proteins/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , TNF Receptor-Associated Factor 2 , Transfection , src Homology DomainsABSTRACT
Jim Jones and Jonestown are discussed from a "political control" point of view. Seven basic techniques of political control are identified: Control of property and income, weakening of family ties, a sociopolitical caste system, control of egression (escape), control of verbal expression, cognitive control and emotional control. Jonestown is identified as a mini-totalitarian state ruled by a delusional and paranoid person.
