Chemokine signaling and functional responses: The role of receptor dimerization and TK pathway activation

A broad array of biological responses, including cell polarization, movemen t, immune and inflammatory responses, and prevention of HIV-1 infection, ar e triggered by the chemokines, a family of structurally related chemoattrac tant proteins that bind to specific seven-transmembrane receptors linked to G proteins. Here we discuss one of the early signaling pathways activated by chemokines, the JAK/STAT pathway. Through this pathway, and possibly in conjunction with other signaling pathways, the chemokines promote changes i n cellular morphology, collectively known as polarization, required for che motactic responses. The polarized cell expresses the chemokine receptors at the leading cell edge, to which they are conveyed by rafts, a cholesterol- enriched membrane fraction fundamental to the lateral organization of the p lasma membrane. Finally, the mechanisms through which the chemokines promot e their effect are discussed in the context of the prevention of HIV-1 infe ction.