Linked Life Data

12842872

Source:http://linkedlifedata.com/resource/pubmed/id/12842872

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2003-9-22
pubmed:abstractText
The Tec family kinase Itk plays a critical role in signal transduction downstream of the T cell antigen receptor and has been implicated in the activation of phospholipase C-gamma1, a key regulator of calcium mobilization and extracellular signal-regulated kinase (ERK) activation. We have shown previously that Itk is regulated by an activating transphosphorylation event in which Tyr-511 in the kinase domain is phosphorylated by Lck (Heyeck, S. D., Wilcox, H. M., Bunnell, S. C., and Berg, L. J. (1997) J. Biol. Chem. 272, 25401-25408). In this study, we present evidence for another mode of regulation for Itk, the autophosphorylation of Tyr-180 in the Src homology 3 (SH3) domain. To investigate the role of Itk trans- and autophosphorylation in T cell signaling, a retroviral transduction system was used to introduce different versions of Itk into Itk-deficient primary T cells. We report that Itk mutated at either the trans- or the autophosphorylation site is unable to fully restore cytokine production and ERK activation in the Itk-deficient cells; Itk-Y511F is severely defective, whereas Itk-Y180F has partial activity. Because phosphorylation at Tyr-180 is predicted to interfere with ligand binding by the SH3 domain, an SH3 point mutant that cannot bind ligand was also examined and found to be unable to restore function to the Itk-/- cells. These data provide new insights into the complex regulation of Itk in primary T cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
37112-21
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Itk phosphorylation sites are required for functional activity in primary T cells.
pubmed:affiliation
Division of Medical Sciences, Harvard University, Cambridge, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.