A novel and functional interaction between cyclophilin A and prolactin receptor.

Precedent data have revealed that peptidyl isomerases can modulate the function of cell-surface receptors, but no such interactions have been previously shown for the members of the cytokine receptor superfamily. We demonstrate here that a functional interaction occurs between the prolactin receptor (PRLR) and peptidyl prolyl cis/trans isomerase cyclophilin A ...
(CypA). CypA was co-immunoprecipitated with the PRLR in vivo from the breast epithelial cell line T47D and Chinese hamster ovary transfectants overexpressing transfected human PRLR. In addition, in vitro binding assays demonstrated a direct interaction of CypA with the PRLR, in the presence or absence of cyclosporine. Co-immunoprecipitation studies also showed an association of CypA with Jak2. Functional analysis revealed that overexpression of CypA inhibited PRL-induced Rac activation, while simultaneously prolonging Jak2 phosphorylation. These proximal actions had profound downstream effects: CypA overexpression significantly enhanced the basal and PRL-stimulated expression from a beta-casein reporter construct. Hence, the interaction between CypA and the PRLR plays a differential regulatory role in the various signaling pathways leading from the PRLR.
Mesh Terms:
Animals, Breast, CHO Cells, Caseins, Cricetinae, Cyclophilin A, Down-Regulation, Epithelial Cells, Humans, Janus Kinase 2, Phosphorylation, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Receptors, Prolactin, Signal Transduction, Transfection, rac1 GTP-Binding Protein
Endocrine
Date: Apr. 02, 2003
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