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. Author manuscript; available in PMC: 2011 Jan 10.
Published in final edited form as: Immunol Rev. 2009 Nov;232(1):195–217. doi: 10.1111/j.1600-065X.2009.00834.x

Figure 4. Model of FcεRI-induced LAT1 and LAT2 multiprotein complexes in mast cells (MCs).

Figure 4

FcεRI stimulation causes LAT1 tyrosine phosphorylation, which allows association with Gads, Grb2, SLP-76, Btk, Vav1, SLAP-130, and phospholipase C-γ (PLC-γ). Structural motifs for interactions are shown. The small adapters Grb2 and Gads bring molecules like son-of-sevenless (SOS) and SLP-76 into the complex. SLP-76 can recruit two additional adapters, SLP-130 and most probably Nck. Other signaling molecules, like Vav1 and Btk, can bind to tyrosine-phosphorylated SLP-76 via their SH2 domains. Like LAT1, LAT2 also becomes tyrosine phosphorylated upon FcεRI stimulation and is also able to recruit Grb2 and SOS. In contrast to LAT1, the adapter LAT2 associates with Vav1 primarily via binding to Grb2. In addition, through a second Grb2-interaction site, the adapter Gab2 may be indirectly recruited to the LAT2 multiprotein complex. Grb2 mediates recruitment of Gab2 via its SH2 domain binding to LAT2 and its SH3 domain binding to the proline-rich region of Gab2. Tyrosine phosphorylation of Gab2 results in the recruitment of the regulatory PI3K subunit p85 via its SH2 domain subsequently leading to PI3K activation.