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The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis.

Trachtenberg A, Pushkarsky T, Heine S, Constant S, Brichacek B, Bukrinsky M - BMC Res Notes (2011)

Bottom Line: However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp.Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA.Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.

View Article: PubMed Central - HTML - PubMed

Affiliation: The George Washington University, Washington, DC 20037, USA. mtmmib@gwumc.edu.

ABSTRACT

Background: Previous studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp). However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression.

Results: Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.

Conclusions: Our results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.

No MeSH data available.


Related in: MedlinePlus

Analysis of Erk activation. Cells with low and high levels of CD147 expression were stimulated (A) or not (C) with CypA or PMA as described in Materials and Methods. Phosphorylated (activated) and total Erks were revealed by Western blotting. Results are presented for one representative experiment out of three performed.
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Figure 2: Analysis of Erk activation. Cells with low and high levels of CD147 expression were stimulated (A) or not (C) with CypA or PMA as described in Materials and Methods. Phosphorylated (activated) and total Erks were revealed by Western blotting. Results are presented for one representative experiment out of three performed.

Mentions: Cell chemotaxis is dependent on signalling events transduced by the chemotactic receptor in response to ligand binding. Interaction of cyclophilin with CD147 induces a number of signalling events, including Ca2+ mobilization and Erk 1/2 activation [3,9]. We analyzed CypA-induced Erk activation in HeLa cells expressing low and high levels of CD147. Consistent with results of the chemotaxis assay, cells with high level of CD147 expression exhibited Erk phosphorylation whereas Erk activation in cells with low level CD147 expression was minimal (Figure 2). Both high and low CD147 expressors equally responded to PMA activation, indicating that low response to eCypA was not due to an internal signalling defect. Despite the fact that the antibodies we used recognize both p42 and p44 forms of Erk, only one Erk form was detected in these experiments. This result may reflect the feature of the HeLa cell line where Erk 1 is expressed at a much lower level than Erk 2 [20]. This result establishes a correlation between the level of CD147 expression and Erk activation in response to eCypA stimulation.


The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis.

Trachtenberg A, Pushkarsky T, Heine S, Constant S, Brichacek B, Bukrinsky M - BMC Res Notes (2011)

Analysis of Erk activation. Cells with low and high levels of CD147 expression were stimulated (A) or not (C) with CypA or PMA as described in Materials and Methods. Phosphorylated (activated) and total Erks were revealed by Western blotting. Results are presented for one representative experiment out of three performed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198701&req=5

Figure 2: Analysis of Erk activation. Cells with low and high levels of CD147 expression were stimulated (A) or not (C) with CypA or PMA as described in Materials and Methods. Phosphorylated (activated) and total Erks were revealed by Western blotting. Results are presented for one representative experiment out of three performed.
Mentions: Cell chemotaxis is dependent on signalling events transduced by the chemotactic receptor in response to ligand binding. Interaction of cyclophilin with CD147 induces a number of signalling events, including Ca2+ mobilization and Erk 1/2 activation [3,9]. We analyzed CypA-induced Erk activation in HeLa cells expressing low and high levels of CD147. Consistent with results of the chemotaxis assay, cells with high level of CD147 expression exhibited Erk phosphorylation whereas Erk activation in cells with low level CD147 expression was minimal (Figure 2). Both high and low CD147 expressors equally responded to PMA activation, indicating that low response to eCypA was not due to an internal signalling defect. Despite the fact that the antibodies we used recognize both p42 and p44 forms of Erk, only one Erk form was detected in these experiments. This result may reflect the feature of the HeLa cell line where Erk 1 is expressed at a much lower level than Erk 2 [20]. This result establishes a correlation between the level of CD147 expression and Erk activation in response to eCypA stimulation.

Bottom Line: However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp.Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA.Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.

View Article: PubMed Central - HTML - PubMed

Affiliation: The George Washington University, Washington, DC 20037, USA. mtmmib@gwumc.edu.

ABSTRACT

Background: Previous studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp). However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression.

Results: Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.

Conclusions: Our results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.

No MeSH data available.


Related in: MedlinePlus