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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3342-3348
CHEMOKINES
Janus kinase 2 is involved in stromal cell-derived
factor-1 -induced tyrosine phosphorylation of focal adhesion
proteins and migration of hematopoietic progenitor cells
Xue-Feng Zhang,
Jian-Feng Wang,
Ewa Matczak,
JoAnn Proper, and
Jerome E. Groopman
From the Division of Experimental Medicine and
Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA.
Stromal cell-derived factor-1 (SDF-1), the ligand for the CXCR4
receptor, is a highly efficacious chemoattractant for CD34+
hematopoietic progenitor cells. However, the SDF-1/CXCR4 signaling pathways that regulate hematopoiesis are still not well defined. This
study reports that SDF-1 can stimulate the tyrosine phosphorylation of Janus kinase 2 (JAK2) and other members of the JAK/signal
transduction and activation of transcription (STAT) family, including
JAK1, tyrosine kinase 2, STAT2, and STAT4 in the human
progenitor cell line, CTS. SDF-1 stimulation of these cells also
enhanced the association of JAK2 with phosphatidylinositol 3 (PI3)-kinase. This enhanced association was abolished by pretreatment
of cells with AG490, a specific JAK2 inhibitor. Furthermore,
pretreatment of CTS cells with AG490 significantly inhibited
SDF-1-induced PI3-kinase activity, and inhibition of JAK2 with
AG490 ablated the SDF-1-induced tyrosine phosphorylation of
multiple focal adhesion proteins (including focal adhesion
kinase, related adhesion focal tyrosine kinase, paxillin,
CrkII, CrkL, and p130Cas). Chemotaxis assays showed that
inhibition of JAK2 diminished SDF-1-induced migration in both CTS
cells and CD34+ human bone marrow progenitor cells. Hence,
these results suggest that JAK2 is required for CXCR4 receptor-mediated
signaling that regulates cytoskeletal proteins and cell migration
through PI3-kinase pathways in hematopoietic progenitor cells.
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