HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zipfel, P. A. Articles by Pendergast, A. M. Search for Related Content PubMed PubMed Citation Articles by Zipfel, P. A. Articles by Pendergast, A. M.

The c-Abl Tyrosine Kinase Is Regulated Downstream of the B Cell Antigen Receptor and Interacts with CD19¹

Patricia A. Zipfel^2,*, Matthew Grove^2,*, Kevin Blackburn, Manabu Fujimoto, Thomas F. Tedder and Ann Marie Pendergast^3,*

^* Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710; Department of Analytical Chemistry, Glaxo Wellcome, Research Triangle Park, NC 27709; and Department of Immunology, Duke University Medical Center, Durham, NC 27710

c-Abl is a nonreceptor tyrosine kinase that we have recently linked to growth factor receptor signaling. The c-Abl kinase is ubiquitously expressed and localizes to the cytoplasm, plasma membrane, cytoskeleton, and nucleus. Thus, c-Abl may regulate signaling processes in multiple subcellular compartments. Targeted deletion or mutation of c-Abl in mice results in a variety of phenotypes, including splenic and thymic atrophy and lymphopenia. Additionally, lymphocytes isolated from specific compartments of c-Abl mutant mice have reduced responses to a variety of stimuli and an increased susceptibility to apoptosis following growth factor deprivation. Despite these observations, little is known regarding the signaling mechanisms responsible for these phenotypes. We report here that splenic B cells from c-Abl-deficient mice are hyporesponsive to the proliferative effects of B cell Ag receptor (BCR) stimulation. The c-Abl kinase activity and protein levels are elevated in the cytosol following activation of the BCR in B cell lines. We show that c-Abl associates with and phosphorylates the BCR coreceptor CD19, and that c-Abl and CD19 colocalize in lipid membrane rafts. These data suggest a role for c-Abl in the regulation of B cell proliferation downstream of the BCR, possibly through interactions with CD19.

This article has been cited by other articles:

				H. Brightbill and M. S. Schlissel The effects of c-Abl mutation on developing B cell differentiation and survival Int. Immunol., May 1, 2009; 21(5): 575 - 585. [Abstract] [Full Text] [PDF]

				R. A. Liberatore and S. P. Goff c-Abl-deficient mice exhibit reduced numbers of peritoneal B-1 cells and defects in BCR-induced B cell activation Int. Immunol., April 1, 2009; 21(4): 403 - 414. [Abstract] [Full Text] [PDF]

				J. J. Gu, N. Zhang, Y.-W. He, A. J. Koleske, and A. M. Pendergast Defective T Cell Development and Function in the Absence of Abelson Kinases J. Immunol., December 1, 2007; 179(11): 7334 - 7343. [Abstract] [Full Text] [PDF]

				G. Chen, I. D. Dimitriou, J. La Rose, S. Ilangumaran, W.-C. Yeh, G. Doody, M. Turner, J. Gommerman, and R. Rottapel The 3BP2 Adapter Protein Is Required for Optimal B-Cell Activation and Thymus-Independent Type 2 Humoral Response Mol. Cell. Biol., April 15, 2007; 27(8): 3109 - 3122. [Abstract] [Full Text] [PDF]

				S. Mumprecht, M. Matter, V. Pavelic, and A. F. Ochsenbein Imatinib mesylate selectively impairs expansion of memory cytotoxic T cells without affecting the control of primary viral infections Blood, November 15, 2006; 108(10): 3406 - 3413. [Abstract] [Full Text] [PDF]

				K. Lin, M. A. Glenn, R. J. Harris, A. D. Duckworth, S. Dennett, J. C. Cawley, M. Zuzel, and J. R. Slupsky c-Abl Expression in Chronic Lymphocytic Leukemia Cells: Clinical and Therapeutic Implications. Cancer Res., August 1, 2006; 66(15): 7801 - 7809. [Abstract] [Full Text] [PDF]

				Y. Lee, K. M. Haas, D. O. Gor, X. Ding, D. R. Karp, N. S. Greenspan, J. C. Poe, and T. F. Tedder Complement Component C3d-Antigen Complexes Can Either Augment or Inhibit B Lymphocyte Activation and Humoral Immunity in Mice Depending on the Degree of CD21/CD19 Complex Engagement J. Immunol., December 15, 2005; 175(12): 8011 - 8023. [Abstract] [Full Text] [PDF]

				T. Jinquan, H. H. Jacobi, C. Jing, A. Millner, E. Sten, L. Hviid, L. Anting, L. P. Ryder, C. Glue, P. S. Skov, et al. CCR3 Expression Induced by IL-2 and IL-4 Functioning as a Death Receptor for B Cells J. Immunol., August 15, 2003; 171(4): 1722 - 1731. [Abstract] [Full Text] [PDF]

				P. J. Woodring, T. Hunter, and J. Y. J. Wang Regulation of F-actin-dependent processes by the Abl family of tyrosine kinases J. Cell Sci., July 1, 2003; 116(13): 2613 - 2626. [Abstract] [Full Text] [PDF]

				M. Dykstra, A. Cherukuri, and S. K. Pierce Rafts and synapses in the spatial organization of immune cell signaling receptors J. Leukoc. Biol., November 1, 2001; 70(5): 699 - 707. [Abstract] [Full Text] [PDF]

				M. Hasegawa, M. Fujimoto, J. C. Poe, D. A. Steeber, C. A. Lowell, and T. F. Tedder A CD19-Dependent Signaling Pathway Regulates Autoimmunity in Lyn-Deficient Mice J. Immunol., September 1, 2001; 167(5): 2469 - 2478. [Abstract] [Full Text] [PDF]

				M. Fujimoto, J. C. Poe, M. Hasegawa, and T. F. Tedder CD19 Amplification of B Lymphocyte Ca2+ Responses. A ROLE FOR Lyn SEQUESTRATION IN EXTINGUISHING NEGATIVE REGULATION J. Biol. Chem., November 21, 2001; 276(48): 44820 - 44827. [Abstract] [Full Text] [PDF]