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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Greer, S. F. Articles by Justement, L. B. Search for Related Content PubMed PubMed Citation Articles by Greer, S. F. Articles by Justement, L. B.

CD45 Function Is Regulated by an Acidic 19-Amino Acid Insert in Domain II That Serves as a Binding and Phosphoacceptor Site for Casein Kinase 2¹

Susanna F. Greer^2,*, Yan-ni Wang^2,*, Chander Raman and Louis B. Justement^3,*

^* Department of Microbiology, Division of Developmental and Clinical Immunology, and Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL 35294

In this study experiments were conducted to elucidate the physical/functional relationship between CD45 and casein kinase 2 (CK2). Immunoprecipitation experiments demonstrated that CK2 associates with CD45 and that this interaction is inducible upon Ag receptor cross-linking in B and T cell lines as well as murine thymocytes and splenic B cells. However, yeast two-hybrid analysis failed to demonstrate a physical interaction between the individual CK2 , ', or subunits and CD45. In contrast, a yeast three-hybrid assay in which either CK2 and or ' and subunits were coexpressed with the cytoplasmic domain of CD45, demonstrated that both CK2 subunits are necessary for the interaction with CD45. Experiments using the yeast three-hybrid assay also revealed that a 19-aa acidic insert in domain II of CD45 mediates the physical interaction between CK2 and CD45. Structure/function experiments in which wild-type or mutant CD45RA and CD45RO isoforms were expressed in CD45-deficient Jurkat cells revealed that the 19-aa insert is important for optimal CD45 function. The ability of both CD45RA and CD45RO to reconstitute CD3-mediated signaling based on measurement of calcium mobilization and mitogen-activated protein kinase activation was significantly decreased by deletion of the 19-aa insert. Mutation of four serine residues within the 19-aa insert to alanine affected CD45 function to a similar extent compared with that of the deletion mutants. These findings support the hypothesis that a physical interaction between the CD45 cytoplasmic domain and CK2 is important for post-translational modification of CD45, which, in turn, regulates its catalytic function.

This article has been cited by other articles:

				S. Kirchberger, O. Majdic, S. Bluml, C. Schrauf, J. Leitner, C. Gerner, W. Paster, N. Gundacker, M. Sibilia, and J. Stockl The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells Blood, August 15, 2008; 112(4): 1240 - 1248. [Abstract] [Full Text] [PDF]

				D. A. Alvarez-Arias and K. S. Campbell Protein Kinase C Regulates Expression and Function of Inhibitory Killer Cell Ig-Like Receptors in NK Cells J. Immunol., October 15, 2007; 179(8): 5281 - 5290. [Abstract] [Full Text] [PDF]

				Y. Wang and P. Johnson Expression of CD45 Lacking the Catalytic Protein Tyrosine Phosphatase Domain Modulates Lck Phosphorylation and T Cell Activation J. Biol. Chem., April 8, 2005; 280(14): 14318 - 14324. [Abstract] [Full Text] [PDF]

				H.-J. Nam, F. Poy, H. Saito, and C. A. Frederick Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45 J. Exp. Med., February 7, 2005; 201(3): 441 - 452. [Abstract] [Full Text] [PDF]