CXCR4信号通路图

CXCR4 is a chemokine r eceptor in the GPCR gene fam ily, and is expr essed by c ells in the immune system and the c entr al nervous system. In r esponse to binding its ligand SDF-1 (str omal c ell-derived factor-1), CXCR4 triggers the m igr ation and r ecruitment of immune cells. This ligand-rec eptor pair may also play a role in development of the nervous system. In addition to acting as a chemokine rec eptor, CXCR4 is a c o-r ec eptor for entry of HIV into T cells and ligands of CXCR4, including SDF-1 may help to bloc k HIV infection. E arly in the infection of an individual, HIV viruses often ar e tr opic for the CCR5 c or eceptor that pr ovides for macr ophage entry, then later in infection ar e tr opic for CXCR4 and T c ell entry. Viruses that are tr opic for CXCR4 ar e generally syncitium for m ing, c ausing T c ells to aggregate and be destroyed at a rapid rate.
CXCR4 induc es downstr eam signaling by sever al differ ent pathways. As a GPCR, CXCR4 binding of SDF-1 activates G-protein mediated signaling, including downstream pathways such as ras, and PI3 kinase. PI3 kinase activated by SDF-1 and CXCR4 plays a r ole in lymphocyte chemotaxis in r esponse to these signals. One endpoint of CXCR4 signaling is the activation of tr anscription factors suc h as AP-1 and chemokine r egulated genes. JAK/STAT signaling pathways also appear to play a role in SDF-1/CXCR4 signaling. Delineation of the signaling mec hanisms utilized by CXCR4 may assist in deter mining the role of CXCR4 in HIV infection and in the immune response.。