Pushkarsky T, Yurchenko V, Sherry B, Bukrinsky M; International Conference on AIDS.
Int Conf AIDS. 2002 Jul 7-12; 14: abstract no. TuPeA4338.
The George Washington University, Washington, DC, United States
BACKGROUND: Cyclophilin A (CyPA) is a ubiquitously distributed intracellular protein belonging to the immunophilin family. CyPA possesses peptidyl-prolyl cis-trans isomerase activity and plays an important role in protein folding. In addition, CyPA is incorporated into HIV-1 virions and regulates an early step of HIV-1 infection. Previously, we demonstrated that CD147 mediates CyPA activity by regulating a post-entry step of HIV-1 infection. Here, we analyzed molecular details of CyPA-CD147 interaction. METHODS: CyPA-induced signaling events in CHO cells stably expressing human CD147 were monitored by phosphorylation of ERK MAPK. Chemotaxis was analyzed using modified Boyden chambers. For one-cycle infection with HIV-1, recombinant viruses pseudotyped with different envelopes and expressing luciferase reporter were used. RESULTS: Expression of CD147 in CHO cells initiated a series of CyPA-dependent signaling events culminating in MAP kinase activation, cell proliferation, and chemotaxis. Importantly, these effects required rotamase activity of CyPA, as CyPA mutants defective in this activity failed to induce signaling events. We also demonstrated that substitution of proline 180 and glycine 181 (a consensus CyPA-binding site) of the CD147 extracellular domain with alanines abrogated signaling and chemotactic activities mediated by CD147 without affecting expression of the mutant protein, indicating that these residues are critical for signaling activity of CD147. However, activity of mutant CD147 in HIV-1 infection was indistinguishable from that of wild-type CD147. CONCLUSIONS: These results identify CD147 as a signaling receptor for CyPA and suggest a novel mechanism for ligand-receptor interactions whereby CyPA initiates signaling by isomerisation of CD147. Signaling capability is not required for CD147 activity in HIV-1 infection of transfected cells, resembling the situation with chemokine receptors.
Publication Types:
Keywords:
- Animals
- Binding Sites
- CHO Cells
- Carrier Proteins
- Chemotaxis
- Cricetinae
- Cyclophilins
- HIV-1
- Humans
- Mitogen-Activated Protein Kinases
- Peptidylprolyl Isomerase
- Proline
- Proteins
- Signal Transduction
- Virion
Other ID:
UI: 102250345
From Meeting Abstracts