|Sartin, James - COLL VET MED, AUBURN|
|Rodrigo, Jose - RAMON Y CAJAL INST|
Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 9, 2007
Publication Date: May 18, 2007
Citation: Elsasser, T.H., Kahl, S., Li, C., Sartin, J.L., Garrett, W.M., Rodrigo, J. 2007. Caveolae-based nitration at the jak-2 kinase 1007 y-1008-y phosphorylation site; a novel regulatory input to signal transduction processing. Endocrinology 148:3803-3813. Available http://endo.endojournals.org. Interpretive Summary: Naturally encountered biological stresses cause changes in metabolism in large part because many of the hormonal signals that regulate metabolism become inoperative. A class of proteins called signal transduction proteins control how cells respond to many hormone signals and as such could be considered prime targets upon which the effects of stress could be imposed. We isolated one of these critical signal transduction proteins called JAK-2 kinase and showed in the present research that this protein becones chemically oxidized during certain stress responses in calves and in this oxidative state, this protein has nitrogen groups attached to it in regions that are critical for the activity of this protein to function properly. In this report we demonstrated that vitamin E could block some of this nitrogen effect/damage and help animals recover from the biochemical effects of stress sooner. The research suggests that many ill effects of immune stress might be staved off if antioxidant treatment were started before periods of known stress encountered by animals, e.g., birth, weaning, and commonly encountered microbe-driven illnesses.
Technical Abstract: With antibodies developed to probe the chemical character of the 1007Y-1008Y phosphorylation epitope of JAK-2 kinase, we demonstrated that this regulatory position can be selectively nitrated in vivo during proinflammatory stress, concomitant with the development of refractoriness in the regulation of insulin-like growth factor-1 (IGF-1) by growth hormone (GH). Evident at the cell membrane and identified in triton-stabile liver homogenates, 1007Y-1008Y-nitrated-JAK-2 colocalized in confocal micrographs and co-precipitated with caveolae proteins. The temporal development of site-specific nitration of regulatory phosphorylation domains of proteins collected in caveolae microenvironments during proinflammatory stress suggests a unique role for nitration in localized signal transduction switching.