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. 2010 Jan 4;285(10):7805–7817. doi: 10.1074/jbc.M109.091173

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FIGURE 9. — Regulation of CXCR4 activity and signaling. A, upon ligand binding, CXCR4 activates a number of signaling cascades resulting in calcium release from intracellular stores and phosphorylation of ERK1/2. B, phosphorylation of CXCR4 by GRK6 (Ser-324/5, Ser-330, and Ser-339) and GRK2 (residues between Ser-346 and Ser-352) resulted in the recruitment of arrestin3 to CXCR4, thereby attenuating G protein activation and calcium release. PLCβ, phospholipase Cβ; PIP₂, phosphatidylinositol disphosphate; IP₃, inositol trisphosphate. C, phosphorylation of CXCR4 by GRK6 (Ser-324/5, Ser-330, and Ser-339) and GRK3 (residues between Ser-346 and Ser-352) resulted in a conformation of arrestin2 that allows for full activation of ERK1/2. In contrast, GRK2 inhibits ERK1/2 activation most likely by regulating the activity of MEK (25).