| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;
Department of Immunology and Rheumatology, Merck Research Laboratories, Rahway, NJ 07065;
Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan;
National Institute for Basic Biology, Aichi, Japan; and
¶ Amgen, Thousand Oaks, CA 91320
Lnk is an adaptor protein expressed primarily in lymphocytes and hemopoietic precursor cells. Marked expansion of B lineage cells occurs in lnk-/- mice, indicating that Lnk regulates B cell production by negatively controlling pro-B cell expansion. In addition, lnk-/- hemopoietic precursors have an advantage in repopulating the hemopoietic system of irradiated host animals. In this study, we show that Lnk overexpression results in impaired expansion of lymphoid precursor cells and altered mature B cell subpopulations. The representation of both B lineage and T lineage cells was reduced in transgenic mice overexpressing Lnk under the control of a lymphocyte-specific expression vector. Whereas the overall number of B and T cells was correlated with Lnk protein expression levels, marginal zone B cells in spleen and B1 cells in the peritoneal cavity were relatively resistant to Lnk overexpression. The C-terminal tyrosine residue, conserved among Lnk family adaptor proteins, was dispensable for the negative regulatory roles of Lnk in lymphocyte development. Our results illuminate the novel negative regulatory mechanism mediated by the Lnk adaptor protein in controlling lymphocyte production and function.
This article has been cited by other articles:
|
|
 |
|
  C. Simon, E. Dondi, A. Chaix, P. de Sepulveda, T. J. Kubiseski, N. Varin-Blank, and L. Velazquez Lnk adaptor protein down-regulates specific Kit-induced signaling pathways in primary mast cells Blood, November 15, 2008; 112(10): 4039 - 4047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gery, S. Gueller, K. Chumakova, N. Kawamata, L. Liu, and H. P. Koeffler Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders Blood, November 1, 2007; 110(9): 3360 - 3364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fitau, G. Boulday, F. Coulon, T. Quillard, and B. Charreau The Adaptor Molecule Lnk Negatively Regulates Tumor Necrosis Factor-{alpha}-dependent VCAM-1 Expression in Endothelial Cells through Inhibition of the ERK1 and -2 Pathways J. Biol. Chem., July 21, 2006; 281(29): 20148 - 20159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Tong, J. Zhang, and H. F. Lodish Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways Blood, June 15, 2005; 105(12): 4604 - 4612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Tong and H. F. Lodish Lnk Inhibits Tpo-mpl Signaling and Tpo-mediated Megakaryocytopoiesis J. Exp. Med., September 7, 2004; 200(5): 569 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iseki, C. Kubo, S.-M. Kwon, A. Yamaguchi, Y. Kataoka, N. Yoshida, K. Takatsu, and S. Takaki Increased Numbers of B-1 Cells and Enhanced Responses against TI-2 Antigen in Mice Lacking APS, an Adaptor Molecule Containing PH and SH2 Domains Mol. Cell. Biol., March 15, 2004; 24(6): 2243 - 2250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Minami, M. Iseki, K. Kishi, M. Wang, M. Ogura, N. Furukawa, S. Hayashi, M. Yamada, T. Obata, Y. Takeshita, et al. Increased Insulin Sensitivity and Hypoinsulinemia in APS Knockout Mice Diabetes, November 1, 2003; 52(11): 2657 - 2665. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
