| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Department of Pediatrics, University of Pittsburgh, School of Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, PA 15213;
Division of Pediatrics, University of Texas-M. D. Anderson Cancer Center, Houston, TX 77030;
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University School of Medicine, Honjo, Kumamoto, Japan;
PRESTO, Japan Science and Technology Corporation, Kawaguchi, Japan;
¶
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan;
||
Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711; and
#
Departments of Psychiatry and Neurobiology, PittArray Microarray Core, University of Pittsburgh, Pittsburgh, PA 15261
Lyn is the only member of the Src family expressed in DT40 B cells, which provide a unique model to study the singular contribution of this protein tyrosine kinase (PTK) family to cell signaling. In these cells, gene ablation of Lyn leads to defective B cell receptor signaling. Complementary DNA array analysis of Lyn-deficient DT40 cells shows that the absence of Lyn leads to down-regulation of numerous genes encoding proteins involved in B cell receptor signaling, proliferation, control of transcription, immunity/inflammation response, and cytoskeletal organization. Most of these expression changes have not been previously associated with Lyn PTK signaling. They include alterations in mRNA levels of germinal center-associated nuclear protein (germinal center-associated DNA primase) (GANP), CD74, CD22, NF-
B, elongation factor 1
, CD79b, octamer binding factor 1, Ig H chain, stathmin, and 
-actin. Changes in GANP expression were also confirmed in Lyn-deficient mice, suggesting that Lyn PTK has a unique function not compensated for by other Src kinases. Because Lyn-deficient mice have impaired development of germinal centers in spleen, the decreased expression of GANP in the Lyn-deficient DT40 cell line and Lyn-deficient mice suggests that Lyn controls the formation and proliferation of germinal centers via GANP. GANP promoter activity was higher in wild-type vs Lyn-deficient cells. Mutation of the PU.1 binding site reduced activity in wild-type cells and had no effect in Lyn-deficient cells. The presence of Lyn enhanced PU.1 expression in a Northern blot. Thus, the following new signaling pathway has been described: Lyn
PU.1GANP.
This article has been cited by other articles:
|
|
 |
|
  W. Carre, X. Wang, T. E. Porter, Y. Nys, J. Tang, E. Bernberg, R. Morgan, J. Burnside, S. E. Aggrey, J. Simon, et al. Chicken genomics resource: sequencing and annotation of 35,407 ESTs from single and multiple tissue cDNA libraries and CAP3 assembly of a chicken gene index Physiol Genomics, May 16, 2006; 25(3): 514 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Hernandez-Hansen, J. D. J. Bard, C. A. Tarleton, J. A. Wilder, C. A. Lowell, B. S. Wilson, and J. M. Oliver Increased Expression of Genes Linked to Fc{epsilon}RI Signaling and to Cytokine and Chemokine Production in Lyn-Deficient Mast Cells J. Immunol., December 15, 2005; 175(12): 7880 - 7888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sakaguchi, T. Kimura, S. Matsushita, S. Fujimura, J. Shibata, M. Araki, T. Sakamoto, C. Minoda, and K. Kuwahara Generation of High-Affinity Antibody against T Cell-Dependent Antigen in the Ganp Gene-Transgenic Mouse J. Immunol., April 15, 2005; 174(8): 4485 - 4494. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
