Proposed mechanism for TAM entrapment at hypoxic sites. Chemoattractant ligands bind to their respective receptors on the surface of TAMs initiating signal transduction events. Activation via phosphorylation of ERK1/2 and p38 MAPK is crucial for chemotaxis. For certain chemoattractant receptors, EKR1/2 and p38 MAPK are inactivated by dephosphorylation due to up-regulation of MKP-1 by hypoxia, which terminates chemotactic signal transduction mechanisms. The signal transduction mechanism for CXCR4 appears not to be affected by hypoxia, suggesting that hypoxia selectively and differentially modulates the expression and function of chemoattractant receptors.