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The pleckstrin homology domain of Gab-2 is required for optimal interleukin-3 signalsome-mediated responses


Reference:

Edmead, C. E., Fox, B. C., Stace, C., Ktistakis, N. and Welham, M. J., 2006. The pleckstrin homology domain of Gab-2 is required for optimal interleukin-3 signalsome-mediated responses. Cellular Signalling, 18 (8), pp. 1147-1155.

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Official URL:

http://dx.doi.org/10.1016/j.cellsig.2005.09.002

Abstract

The adaptor protein Gab-2 coordinates the assembly of the IL-3 signalsome comprising Gab-2, Grb2, Shc, SHP-2 and PI3K. To investigate the role of the pleckstrin homology domain of Gab-2 in this process, epitope-tagged wild type Gab-2 (WTGab-2), Gab-2 lacking its PH domain (ΔPHGab-2) and the Gab-2 PH domain alone (PHGab-2) were inducibly expressed in IL-3-dependent BaF/3 cells. Expression of ΔPHGab-2 reduced IL-3-dependent proliferation and long-term activation of ERK1 and 2 and PKB by IL-3. While we demonstrate that the Gab-2 PH domain can bind PI(3,4,5)P3, it is dispensable for Gab-2 membrane localisation, tyrosine phosphorylation and signalsome formation. Rather, the proline-rich motifs of Gab-2 appear to contribute to the constitutive membrane localisation we observe, independently of tyrosine phosphorylation or the PH domain. Taken together, these findings suggest that once Gab-2 is tyrosine phosphorylated its PH domain is required for the optimal stabilisation of the signalsome, enabling full activation of downstream signals.

Details

Item Type Articles
CreatorsEdmead, C. E., Fox, B. C., Stace, C., Ktistakis, N. and Welham, M. J.
DOI10.1016/j.cellsig.2005.09.002
DepartmentsFaculty of Science > Pharmacy & Pharmacology
RefereedYes
StatusPublished
ID Code7776

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