Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation.
A broad array of biological responses, including cell polarization, movement, immune and inflammatory responses, and prevention of HIV-1 infection, are triggered by the chemokines, a family of structurally related chemoattractant 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 in cellular morphology, collectively known as polarization, required for chemotactic 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 plasma membrane. Finally, the mechanisms through which the chemokines promote their effect are discussed in the context of the prevention of HIV-1 infection.
Mellado
M
M
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus de Cantoblanco, Madrid, E-28049 Spain.
Rodríguez-Frade
J M
JM
Mañes
S
S
Martínez-A
C
C
D002465:Cell Movement; D016764:Cell Polarity; D018925:Chemokines / Q000494:pharmacology / Q000502:physiology*; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000502:physiology; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D021962:Membrane Microdomains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D018925:Chemokines; D019204:GTP-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D014157:Transcription Factors