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Cyclophilin A is required for M‐CSF‐dependent macrophage proliferation
Author(s) -
SànchezTilló Ester,
Wojciechowska Marta,
Comalada Monica,
Farrera Consol,
Lloberas Jorge,
Celada Antonio
Publication year - 2006
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200535270
Subject(s) - biology , kinase , microbiology and biotechnology , cyclin dependent kinase , mapk/erk pathway , cell growth , cell cycle , calcineurin , phosphatase , cyclophilin a , pin1 , cyclin , phosphorylation , mitogen activated protein kinase , protein kinase a , cyclin dependent kinase 2 , cyclin a , biochemistry , cell , enzyme , isomerase , medicine , transplantation
Abstract The immunosuppressor sanglifehrin A (SfA) is a member of a family of immunophilin cyclophilin A‐binding molecules and does not inhibit calcineurin activity. Sanglifehrin A inhibits M‐CSF‐dependent macrophage proliferation by arresting the G1 phase of the cell cycle but does not affect cell viability. This immunosuppressor exerts its action on proliferation by inactivating cyclin‐dependent kinase 2 (Cdk2) activity. Moreover, c‐myc expression is also repressed. In the early steps of M‐CSF signaling, SfA inhibits the phosphorylation of Raf‐1 and the external regulated kinases (ERK)1/2 and mitogen‐activated protein kinase phosphatase‐1, which are required for proliferation. The effects of SfA are not related to a block of the proteosome activity. These data show that immunophilin contributes to M‐CSF‐dependent proliferation through activation of the Raf‐1/MEK/ERK pathway and the regulation of Cdk activities, which is required for cell cycle progression.