Receptor dimerization: A key step in chemokine signaling

Chemokines exert their effects through their interaction with seven transme mbrane domain receptors coupled to G-proteins, GPCRs. Such receptor ligatio n leads to the regulation of numerous activities where chemokines play a ke y role, including hematopoiesis, T-cell activation, angiogenesis, inflammat ory diseases or HIV-1 infection. Here we discuss the molecular mechanisms t hat underlie chemokine receptor activation. As occurs with other GPCRs, che mokines initiate the signaling cascades by inducing receptor dimerization. This dimerization enables the activation of the JAK/STAT pathway which allo ws the subsequent triggering of G-protein dependent signaling events. This mechanism provides a new context to explain some of the activities exerted by chemokines and introduces new targets for the development of drugs to fi ght those diseases were chemokines are implicated, such as inflammation and AIDS.