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The Related Adhesion Focal Tyrosine Kinase (RAFTK) Is Tyrosine
Phosphorylated and Participates in Colony-Stimulating
Factor-1/Macrophage Colony-Stimulating Factor Signaling in
Monocyte-Macrophages
William C. Hatch,
Ramesh K. Ganju,
Dananagoud Hiregowdara,
Shalom Avraham, and
Jerome E. Groopman
From the Divisions of Experimental Medicine and Hematology/Oncology,
Harvard Institutes of Medicine, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA.
RAFTK, a novel nonreceptor protein kinase, has been shown to be
involved in focal adhesion signal transduction pathways in neuronal
PC12 cells, megakaryocytes, platelets, and T cells. Because focal
adhesions may modulate cytoskeletal functions and thereby alter
phagocytosis, cell migration, and adhesion in monocyte-macrophages, we
investigated the role of RAFTK signaling in these cells. RAFTK was
abundantly expressed in THP1 monocytic cells as well as in primary
alveolar and peripheral blood-derived macrophages. Colony-stimulating factor-1 (CSF-1)/macrophage colony-stimulating factor
(M-CSF) stimulation of THP1 cells increased the tyrosine
phosphorylation of RAFTK; similar increases in phosphorylation were
also detected after lipopolysaccharide stimulation. RAFTK was
phosphorylated with similar kinetics in THP1 cells and peripheral
blood-derived macrophages. Immunoprecipitation analysis showed
associations between RAFTK and the signaling molecule
phosphatidylinositol-3 (PI-3) kinase. PI-3 kinase enzyme activity also
coprecipitated with the RAFTK antibody, further confirming this
association. The CSF-1/M-CSF receptor c-fms and RAFTK appeared
to associate in response to CSF-1/M-CSF treatment of THP1 cells.
Inhibition of RAFTK by a dominant-negative kinase mutant reduced
CSF-1/M-CSF-induced MAPK activity. These data indicate that RAFTK
participates in signal transduction pathways mediated by CSF-1/M-CSF, a
cytokine that regulates monocyte-macrophage growth and function.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3967-3973
© 1998 by The American Society of Hematology.
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