Fig. 5

Signaling pathways of radiation on TAMs. Radiation increases the level of CXCL12 which then binds to CXCR4, a kind of G-protein-coupled receptor (GPCR). Similarly, CCL2 and its receptor, CCR2 are also activated by radiation. Next, the receptor undergoes a second conformational change that activates the intracellular trimeric G protein by the dissociation of Gα subunit from the Gβ/Gγ dimer. Then, the phosphatidylinositide 3-kinases (PI3Ks) can be activated by both Gβ/γ and Gα subunits. PI3Ks regulate gene transcription, migration, and adhesion of TAMs by the phosphorylation of AKT and of several focal adhesion components. In addition, Gα subunit also activates the Ras and Rac/Rho pathways, leading to the phosphorylation of ERK. Activated ERK can phosphorylate and regulate other cellular proteins, as well as translocate into the nucleus and phosphorylate and regulate transcription factors, leading to migration, proliferation, and cytokines expression of TAMs. Gβ/Gγ dimer also activates JAK/STAT signaling pathway to promote changes in cell morphology leading to chemotactic responses. Of note, CSF-1/CSF-1R activates all the three signaling pathways we discussed above. Parts of this figure were drawn with aid of Servier Medical Art (http://www.servier.com), licensed under a Creative Commons Attribution 3.0 Unported License