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Publication : Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor protein, Lnk.

First Author  Takaki S Year  2002
Journal  J Exp Med Volume  195
Issue  2 Pages  151-60
PubMed ID  11805142 Mgi Jnum  J:76219
Mgi Id  MGI:2178875 Doi  10.1084/jem.20011170
Citation  Takaki S, et al. (2002) Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor protein, Lnk. J Exp Med 195(2):151-60
abstractText  Hematopoietic stem cells (HSCs) give rise to variety of hematopoietic cells via pluripotential progenitors and lineage-committed progenitors and are responsible for blood production throughout adult life. Amplification of HSCs or progenitors represents a potentially powerful approach to the treatment of various blood disorders and to applying gene therapy by bone marrow transplantation. Lnk is an adaptor protein regulating the production of B cells. Here we show that Lnk is also expressed in hematopoietic progenitors in bone marrow, and that in the absence of Lnk, the number and the hematopoietic ability of progenitors are significantly increased. Augmented growth signals through c-Kit partly contributed to the enhanced hematopoiesis by lnk-/- cells. Lnk was phosphorylated by and associated with c-Kit, and selectively inhibited c-Kit-mediated proliferation by attenuating phosphorylation of Gab2 and activation of mitogen-activated protein kinase cascade. These observations indicate that Lnk plays critical roles in the expansion and function of early hematopoietic progenitors, and provide useful clues for the amplification of hematopoietic progenitor cells.
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