title: Tec kinase stimulates cell survival in transfected Hek293T cells and is regulated by the anti-apoptotic growth factor IGF-I in human neutrophils.
abstract: OBJECTIVE
  Previously, we showed that the phosphatidylinositol-3 kinase (PI(3)K) pathway mediates the anti-apoptotic effects of IGF-I in human neutrophils independently of its down-stream target Akt. In this study, we investigated whether IGF-I regulates Tec kinase, an alternative down-stream target of PI(3)K, in neutrophils and whether this molecule is able to affect apoptosis.
  
  
  METHODS
  We investigated the translocation of Tec kinases in neutrophils after stimulation with IGF-I. Furthermore, we transiently and stably transfected Hek293T cells with constructs expressing different forms of Tec kinase and measured the level of cell survival and apoptosis/necrosis through trypan blue exclusion test and Annexin-V/propidium iodide labelling, respectively.
  
  
  RESULTS
  We show that IGF-I stimulates the translocation of Tec kinase to the membrane in neutrophils in a PI(3)K dependent matter. Overexpression of Tec kinase augments cell survival by inhibition of necrosis. The pro-survival effect is attenuated by the deletion of the kinase domain but not by inactivation of this domain by a single amino acid substitution.
  
  
  CONCLUSIONS
  Tec kinase can act as a prosurvival factor and is regulated by IGF-I in human neutrophils through PI(3)K activation.
authors.affiliation: Center for Neurosciences, Department of Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium. Ehimpe@gmail.com
authors.forename: E
authors.initials: E
authors.lastname: Himpe
authors.forename: S A
authors.initials: SA
authors.lastname: Abdul Rahim
authors.forename: P
authors.initials: P
authors.lastname: Verdood
authors.forename: H
authors.initials: H
authors.lastname: Mano
authors.forename: R
authors.initials: R
authors.lastname: Kooijman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014162:Transfection
chemical_list: D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt