NDLI: The cytokine midkine and its receptor RPTPÎ¶ regulate B cell survival in a pathway induced by CD74.

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The cytokine midkine and its receptor RPTPÎ¶ regulate B cell survival in a pathway induced by CD74.

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The cytokine midkine and its receptor RPTPÎ¶ regulate B cell survival in a pathway induced by CD74.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zelman-Toister, Einat Maharshak, Nitsan Binsky-Ehrenreich, Inbal Shachar, Idit Harroch, Sheila Gordin, Maya Hazan-Halevy, Inbal Herishanu, Yair Bucala, Richard Haran, Michal Shvidel, Lev Cohen, Sivan Shoshana, Or-yam Leng, Lin
Description	Country affiliation: Israel Author Affiliation: Cohen S ( Department of Immunology, Weizmann Institute of Science, Rehovot, Israel)
Abstract	Lasting B cell persistence depends on survival signals that are transduced by cell surface receptors. In this study, we describe a novel biological mechanism essential for survival and homeostasis of normal peripheral mature B cells and chronic lymphocytic leukemia cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase Î¶ (RPTPÎ¶). We demonstrate that MK initiates a signaling cascade leading to B cell survival by binding to RPTPÎ¶. In mice lacking PTPRZ, the proportion and number of the mature B cell population are reduced. Our results emphasize a unique and critical function for MK signaling in the previously described MIF/CD74-induced survival pathway. Stimulation of CD74 with MIF leads to c-Met activation, resulting in elevation of MK expression in both normal mouse splenic B and chronic lymphocytic leukemia cells. Our results indicate that MK and RPTPÎ¶ are important regulators of the B cell repertoire. These findings could pave the way toward understanding the mechanisms shaping B cell survival and suggest novel therapeutic strategies based on the blockade of the MK/RPTPÎ¶-dependent survival pathway.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1101468
Journal	The Journal of Immunology
Issue Number	1
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Differentiation, B-lymphocyte Immunology B-lymphocytes Cytokines Histocompatibility Antigens Class Ii Membrane Glycoproteins Receptor-like Protein Tyrosine Phosphatases, Class 2 Receptors, Growth Factor Signal Transduction Animals Genetics Metabolism Cell Line, Tumor Cell Survival Gene Expression Regulation Mice Mice, Knockout Proto-oncogene Proteins C-met Spleen Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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