Axl is a tyrosine kinase receptor that is important for hematopoiesis, the innate immune response, platelet aggregation, engulfment of apoptotic cells and cell survival. Binding of growth arrest-specific protein 6 (Gas6) activates Axl signaling, but the mechanism of inactivation of the Axl receptor is poorly understood. In the present study, we show that IQGAP1 modulates Axl signaling. IQGAP1 is a scaffold protein that integrates cell signaling pathways by binding several growth factor receptors and intracellular signaling molecules. Our in vitro analysis revealed a direct interaction between the IQ domain of IQGAP1 and Axl. Analysis by both immunoprecipitation and proximity ligation assays demonstrated an association between Axl and IQGAP1 in cells and this interaction was decreased by Gas6. Unexpectedly, reducing IQGAP1 levels in cells significantly enhanced the ability of Gas6 to stimulate both Axl phosphorylation and activation of Akt. Moreover, IQGAP1 regulates the interaction of Axl with the epidermal growth factor receptor. Our data identify IQGAP1 as a previously undescribed suppressor of Axl and provide insight into regulation of Axl function.
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Cover Image
Cover Image
In this issue, Keith Willison reviews of the structure and evolution of eukaryotic CCT (chaperonin-containing TCP-1) and how it effects actin folding. The cover image shows a space-fill model of the CCT3/γ apical domain with its solvent-accessible-binding surface highlighted in brown and a stretch of bound poly-Gln β-strand occupying the long stretch of anchoring sites. For further details, see pages 3009–3034. Image kindly provided by Miriam Eisenstein (Weizmann Institute for Science).
IQGAP1 binds the Axl receptor kinase and inhibits its signaling
Laëtitia Gorisse, Zhigang Li, Andrew C. Hedman, David B. Sacks; IQGAP1 binds the Axl receptor kinase and inhibits its signaling. Biochem J 15 October 2018; 475 (19): 3073–3086. doi: https://doi.org/10.1042/BCJ20180594
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