Induction of Raf kinase inhibitor protein contributes to macrophage differentiation

Biochemical and Biophysical Research Communications
Marion M SchuiererThomas Langmann

Abstract

Differential gene expression analysis of human blood monocytes has identified the Raf kinase inhibitor protein (RKIP) as a continuously upregulated gene in macrophage and dendritic cell maturation. Using realtime RT-PCR and Western blot analysis we were able to confirm the initial DNA-microarray findings of RKIP induction on mRNA and protein levels. RKIP upregulation in primary cells and overexpression in THP-1 cells did not alter ERK activity but strongly reduced the amount of the NFkappaB subunit p65 in the nucleus. mRNA levels and cell surface expression of maturation markers including the integrin CD11c and the scavenger receptor CD36 were significantly increased in RKIP transfected THP-1 cells. Our data show for the first time that RKIP is upregulated during macrophage and dendritic cell differentiation on mRNA and protein levels and we conclude that RKIP contributes to the monocytic differentiation process via inhibition of the NFkappaB signaling cascade independent from the canonical Ras/Raf/MEK/ERK pathway.

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Citations

Apr 2, 2008·Cell Research·Alexey E Granovsky, Marsha Rich Rosner
Dec 23, 2008·Biochemical and Biophysical Research Communications·Katharina StoeckerThomas Langmann
Sep 11, 2008·Expert Opinion on Therapeutic Targets·Lingchun ZengMarsha Rich Rosner
Jun 14, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyle T Wright, Anthony T Vella
Nov 21, 2019·International Journal of Molecular Sciences·Armin ZebischHeinz Sill
Nov 18, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Antoine MénoretAnthony T Vella
Mar 11, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Martha Lappas
Feb 10, 2011·Cancer Research·Fahd Al-MullaWalter Kolch

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