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. 2014 Nov 21;9(11):e113679. doi: 10.1371/journal.pone.0113679

Figure 5. Location of FAK in the GPVI pathway.

Figure 5

GPVI activation with CRP triggers FcRγ-chain ITAM phosphorylation through Fyn and Lyn, which recruits and activates Syk, initiating a LAT signalosome involving LAT, SLP-76, Gads, PI3-K, Btk, Rac1 and PLCγ2. FAK is downstream of SFKs, Syk, PI3-K and Btk but upstream of Rac1 and PLCγ2 following GPVI ligation. Activated PLCγ2 produces secondary messengers, IP3 and DAG that induce Ca2+ mobilization and PKC activation, respectively, allowing FAK activation and integrin αIIbβ3 engagement, which is also known to regulate FAK activity. FAK also regulates the NOX1 modulator, Rac1, which along with Hic-5, leads to the activation of NOX1, resulting in ROS generation. Key proteins investigated in this study are shaded.