Cyclophilin A is required for M-CSF-dependent macrophage proliferation.

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.

journal_name

Eur J Immunol

authors

Sànchez-Tilló E,Wojciechowska M,Comalada M,Farrera C,Lloberas J,Celada A

doi

10.1002/eji.200535270

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

2515-24

issue

9

eissn

0014-2980

issn

1521-4141

journal_volume

36

pub_type

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