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.

DESIGN:

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.

CONCLUSION:

Tec kinase can act as a prosurvival factor and is regulated by IGF-I in human neutrophils through PI(3)K activation.

• Authors: E Himpe, S A Abdul Rahim, P Verdood, H Mano, R Kooijman
• Journal: Cellular signalling (Cell Signal) Vol. 25 Issue 3 Pg. 666-73 (Mar 2013) ISSN: 1873-3913 [Electronic] England
• PMID: 23261945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Recombinant Proteins
• Insulin-Like Growth Factor I
• Phosphatidylinositol 3-Kinases
• Tec protein-tyrosine kinase
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• HEK293 Cells
• Humans
• Insulin-Like Growth Factor I (genetics, metabolism, pharmacology)
• Mice
• Neutrophils (cytology, drug effects, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Protein-Tyrosine Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Recombinant Proteins (biosynthesis, genetics, pharmacology)
• Transfection