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. Author manuscript; available in PMC: 2011 Nov 1.
Published in final edited form as: Immunol Rev. 2010 Nov;238(1):195–215. doi: 10.1111/j.1600-065X.2010.00962.x

Fig. 2. The SLAM-SAP-Fyn signaling axis during iNKT cell development.

Fig. 2

‘Selecting’ DP thymocytes and iNKT ‘precursor’ cells communicate via invariant TCR-CD1d and SLAM family (SLAM, Ly108) interactions. Engagement of the SLAM family receptors at the cell surface leads to recruitment of the adaptor molecule SAP and the Src family tyrosine kinase Fyn. The SLAMf receptor-SAP-Fyn signaling complex triggers activation of NFκB via protein kinase θ (PKCθ) and Bcl10. Additionally, SLAMf receptor-SAP-Fyn signaling also phosphorylates and recruits the SH2 domain–containing inositol phosphatase (SHIP), Dok1/2 adaptor proteins, and the Ras GTPase-activating protein (RasGAP). By binding to RasGAP, Dok1/2 inhibits Ras-MAPK activation. It is possible that SLAMf receptor-induced signals cooperate with those induced by the invariant TCR to modulate NFκB-Ras pathway activity in a manner required for iNKT cell development.