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Activation of JAK2 in human vascular endothelial cells by granulocyte-
macrophage colony-stimulating factor
R Soldi, L Primo, MF Brizzi, F Sanavio, M Aglietta, N Polentarutti, L Pegoraro, A Mantovani and F Bussolino
Dipartimento di Genetica, Biologia e Chimica Medica, Torino, Italy.
Besides the regulation of hematopoiesis, granulocyte-macrophage colony-
stimulating factor (GM-CSF)induces the expression of a functional program
in endothelial cells (ECs) related to angiogenesis and to their survival in
the bone marrow microenvironment. ECs express specific GM- CSF
high-affinity binding sites, which mediate the proliferative and migratory
response. We now report that ECs express the alpha and beta subunits of
GM-CSF receptor (GM-CSFR), and that GM-CSF is able to activate the Janus
kinase (JAK)2, a member of the cytosolic tyrosine kinase family, which is
known to mediate signals of several non- tyrosine kinase receptors. JAK2
tyrosine phosphorylation, as well as activation of its catalytic activity,
is induced by subnanomolar concentrations of GM-CSF and occurs within 3
minutes of stimulation and persists at least for 10 minutes. The effect is
specific as inferred by the lack of effect of heat-inactivated GM-CSF or
neutralized by specific antibodies and by the finding that interleukin-5,
which utilizes a specific alpha chain and the same beta chain of GM-CSFR,
does not phosphorylate JAK2. Furthermore, we show that the amount of JAK2
physically associated with GM-CSFR beta chain is increased after GM-CSF
stimulation and that GM-CSF triggers both beta chain and JAK2 tyrosine
phosphorylation. Taken together, these results suggest that biologic
activities of GM-CSF in vascular endothelium may, in part, be elicited by
GM-CSFR-mediated JAK2 activation.
Volume 89,
Issue 3,
pp. 863-872,
02/01/1997
Copyright © 1997 by The American Society of Hematology
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