Ectophosphorylation of CD36 regulates cytoadherence of Plasmodium falciparum to microvascular endothelium under flow conditions
| Autor: | Naili Liu, Sorrnchai Looareesuwan, Christine L. Flatt, Bradley J. Berger, Holly L. Hoang, Laura Montes, Bryan G. Yipp, May Ho, Kristine Lee, Tara MacRae, Stephen M. Robbins |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD36 Antigens
Threonine Erythrocytes CD36 Immunology Phosphatase Plasmodium falciparum Biology Microbiology 3T3 cells Mice parasitic diseases medicine Cell Adhesion Animals Humans Src family kinase Phosphorylation Cell adhesion Skin Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Adhesion Alkaline Phosphatase Molecular biology Capillaries Protein Structure Tertiary Infectious Diseases medicine.anatomical_structure Pyrimidines src-Family Kinases Ectodomain Levamisole embryonic structures Mutation biology.protein NIH 3T3 Cells Pyrazoles Parasitology Endothelium Vascular Antibodies Phospho-Specific |
| Zdroj: | Infection and immunity. 73(12) |
| ISSN: | 0019-9567 |
| Popis: | The adhesion of Plasmodium falciparum -infected erythrocytes (IRBCs) to human dermal microvascular endothelial cells (HDMECs) under flow conditions is regulated by a Src family kinase- and alkaline phosphatase (AP)-dependent mechanism. In this study, we showed that the target of the phosphatase activity is the ectodomain of CD36 at threonine-92 (Thr 92 ). Mouse fibroblasts (NIH 3T3 cells) transfected with wild-type CD36 or a mutant protein in which Thr 92 was substituted by Ala supported the rolling and adhesion of IRBCs. However, while the Src family kinase inhibitors PP1 and PP2 and the specific AP inhibitor levamisole significantly reduced IRBC adhesion to wild-type CD36 transfectants as with HDMECs, the inhibitors had no effect on IRBC adhesion to the mutant cells. Using a phosphospecific antibody directed at a 12-amino-acid peptide spanning Thr 92 , we demonstrated directly that CD36 was constitutively phosphorylated and could be dephosphorylated by exogenous AP. Endothelial CD36 was likewise constitutively phosphorylated. The phosphospecific antibody inhibited IRBC adhesion to HDMECs that could be reversed by preincubating the antibody with the phosphorylated but not the nonphosphorylated peptide. Pretreatment of HDMECs with AP abrogated the effect of PP1 on IRBC adhesion. Collectively, these results are consistent with a critical role for CD36 dephosphorylation through Src family kinase activation in regulating IRBC adhesion to vascular endothelium. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|