Human chemokine receptor CCR3 (hCCR3) is highly expressed on eosinophils and binds multiple chemokine ligands such as eotaxin (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), and MCP-4 (CCL13) with high affinity [38].
By taking this general approach of Ras hyper-activation, we have recapitulated the excessive activation of the Ras pathway in breast cancer, which is induced in patients by multiple RTK ligands such as epidermal growth factor (EGF) [ 1, 27, 28, 47, 48].
RAGE binds to multiple families of ligands, such as advanced glycation end products (AGEs), S100s, and amphoterin, and plays a key role in diabetes, inflammation, and cancer [5], [10].
Cells adhere specifically to ECM via focal adhesions, where receptors on cell membrane form multiple bonds with ligands such as the ECM protein fibronectin on the extracellular side [10], while connecting with the actin cytoskeleton via a cytoplasmic adhesion plaque composed of many different proteins on the intracellular side [11].
Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition.
Among its multiple biological properties, UG binds hydrophobic ligands, such as progesterone and prostaglandins, and seems to play a homeostatic role against oxidative damage, inflammation, autoimmunity and cancer [ 34].
Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal.
123 The Wnt signaling pathway works in a coordinated manner with other transmembrane signals, including multiple ligands, antagonists, receptors, coreceptors, and transcriptional mediators, such as β-catenin.
Apoptosis initiates when BH3-only ligands, such as Bim, engage multiple Bcl-2 homologues, which liberate Bak to execute mitochondrial membrane opening [ 35].
