The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published 14 January 2002. doi:10.1084/jem.20011170
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© Rockefeller University Press, 0022-1007/2002/1/151/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 2, January 21, 2002 151-160

Original Article

Enhanced Hematopoiesis by Hematopoietic Progenitor Cells Lacking Intracellular Adaptor Protein, Lnk

Satoshi Takaki, Hatsue Morita, Yoshinari Tezuka and Kiyoshi Takatsu

Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

Address correspondence to Satoshi Takaki, Division of Immunology, Dept. of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-5449-5264; Fax: 81-3-5449-5407; E-mail: takakis{at}ims.u-tokyo.ac.jp

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.

Key Words: bone marrow transplantation • hematopoietic progenitors • c-Kit • stem cell factor • Gab2


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