Is Dimerization Of Chemokine Receptors Functionally Relevant?

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Science's STKE  16 Oct 2001:
Vol. 2001, Issue 104, pp. pe34
DOI: 10.1126/stke.2001.104.pe34


  • Fig. 1.

    Presumed mechanisms of calcium mobilization by G protein-coupled and tyrosine kinase-linked receptors. As shown on the right (designated "fast"), chemokines bind to seven transmembrane-domain receptors and induce an immediate conformational change. Subsequently, the pertussis toxin-sensitive Gi protein dissociates from the receptor and its βγ subunits rapidly recruit and activate phospholipase C-β (PLC-β) leading to fast calcium mobilization through inositol trisphosphate (IP3). By contrast, growth factor receptors, as shown on the left (designated "slow"), first undergo ligand-induced dimerization, followed by transphosphorylation of the cytoplasmic domains thereby forming docking sites for downstream effectors such as phosphatidylinositide 3′-OH kinase (PI3K) and phospholipase C-γ (PLC-γ). PLC-γ is then also phosphorylated at tyrosine residues, and its subsequent association with the membrane is enhanced by phosphatidylinositol trisphosphate (PIP3), the product of PI3K. This process is slow. The rapid changes in intracellular calcium following chemokine stimulation are therefore better explained by the straightforward G protein-dependent activation of PLC-β rather by a mechanism that requires first receptor dimerization and then several other steps, including activation of JAK kinases, before G proteins get into action.

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