The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Raman, C.
Right arrow Articles by Kimberly, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Raman, C.
Right arrow Articles by Kimberly, R. P.
The Journal of Immunology, 1998, 161: 5817-5820.
Copyright © 1998 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Differential CD5-Dependent Regulation of CD5-Associated CK2 Activity in Mature and Immature T Cells: Implication on TCR/CD3-Mediated Activation1

Chander Raman2 and Robert P. Kimberly

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, AL 35294


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results and Discussion
 References
 
CD5 attenuates TCR-induced signals in immature thymocytes but functions as a costimulatory molecule potentiating TCR/CD3-mediated activation in mature, peripheral T cells. We have recently shown that the serine/threonine kinase, casein kinase 2 (CK2), a major regulator of cell growth and signaling, associates with and is activated by CD5. Therefore, we tested the possibility that differential regulation of CK2 activity by CD5 may be associated with these differences in CD5 modulation of TCR signaling. Consistent with our hypothesis, CD5-specific cross-linking activated associated CK2 in thymocytes but not active in mature splenocytes. Differential regulation of CD5-associated CK2 provides, for the first time, a potential mechanism for the differential effects of CD5 signaling in immature and mature cells. We propose that CD5 modulates Ag receptor activity through developmentally regulated activation of CD5-associated CK2.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results and Discussion
 References
 
CD5 is expressed before TCR/CD3 early in T cell development, and its level of expression increases as development progresses (1). In immature T cells from thymus, CD5 attenuates TCR/CD3-mediated signaling (2). CD4 or CD8 single positive thymocytes from CD5-/- mice exhibit greater intracellular calcium mobilization and proliferation to CD3 induced signals as well hyperphosphorylation of vav, phospholipase C-{gamma} (PLC-{gamma}),3 and the PLC-{gamma}-associated proteins, pp35/36. In contrast, CD5 provides costimulatory function in mature T cells by potentiating CD3 or CD28 stimulation (3, 4, 5, 6, 7). The mechanisms underlying the differential effects of CD5 signaling in immature and mature T cells are presently unknown.

Following TCR activation, CD5 is rapidly phosphorylated on tyrosyl residues probably by the src family tyrosine kinase, p56lck (8, 9). In contrast, CD5 ligation leads to only serine phosphorylation of its cytoplasmic domain. We recently demonstrated that the serine/threonine kinase, casein kinase 2 (CK2), constitutively associates with distal end of CD5 cytoplasmic domain in normal and transformed cells (10). CK2 is a major regulator of development, cell growth, cell division, and signal transduction pathways (11). The lethality of CK2 deletion in Saccharomyces cerevisiae and the conservation of CK2 through evolution suggest that it is a critical enzyme in cell regulation (12). This unexpected observation of CK2 association with CD5 suggested that CK2 might also be involved in regulating membrane proximal signaling events (11, 13).

CK2 associated with CD5 was inactive in resting cells and was activated by ligation of CD5, consistent with previous reports of an inducible serine kinase activity associated with CD5 (14). CK2 associated with CD5 was not activated by TCR or B cell receptor cross-linking in T and B cell lines. The holoenzyme CK2 consists of catalytic subunits, {alpha} and {alpha}', and a regulatory subunit, ß, in the tetrameric configuration of {alpha}2ß2, {alpha}{alpha}'ß2, or {alpha}'2ß2 (11). CK2 interacts with CD5 via the ß subunit as it does with p53 and the nuclear protein Nopp140 (15, 16). In vitro kinase assays indicated that CK2 phosphorylates CD5 at Ser459 and Ser461, which comprise overlapping CK2 phosphorylation motifs.

The association of CD5 with inactive kinase, and the ability of CD5 to activate CK2 in a receptor-specific fashion, suggested the possibility that the differential effects of CD5 signaling in immature and mature thymocytes might reflect differential regulation of CK2 activity. Unlike CD5 regulation of cytosolic CK2, we show developmental stage-specific CD5-dependent regulation of CD5-associated CK2. These results provide the first evidence for a potential mechanism to explain the opposite effects of CD5 signaling in immature and mature thymocytes.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results and Discussion
 References
 
Cell lines and mice and reagents

Murine B-lymphoma, CH12, and human T-leukemia cell line, Jurkat, were maintained as described previously (10). Murine spleens and thymuses were obtained from 10- to 16-wk-old BALB/c mice (The Jackson Laboratories, Bar Harbor, ME). Anti-mouse CD5 (53-7.3), anti-mouse CD3{epsilon} (145-2C11), anti-human CD19 (HIB19), and control rat IgG2a were obtained from PharMingen (San Diego, CA). Anti-human CD5 (LT1) was from Biodesign International (Kennebunk, ME), and anti-CD5 rabbit serum to CD5 cytoplasmic tail peptide 456-DNSSDSDYDLHGAQRL-471 was developed in our laboratory. Rabbit antisera to CK2{alpha} and ß were gifts from Dr. David Litchfield (Manitoba Institute of Cell Biology).

Immunoprecipitation and Western blot analysis

Cells were stimulated for 5 min with 20 µg/2 x 107 cells anti-CD5 mAb, anti-CD3, or isotype control Ab and lysed in lysis buffer (2 x 107 cells/ml) (10). Lysates prepared from CH12 cells (1 x 107), splenocytes (2 x 107), or thymocytes (1.2 x 107) were immunoprecipitated with agarose conjugated anti-mouse CD5 or agarose-conjugated rat IgG2a, and lysates from Jurkat cells (1 x 107) were incubated with anti-human CD5, anti-mouse CD19 (IgG1 isotype control), followed by precipitation with protein G agarose. Cytosolic CK2 was immunoprecipitated with anti-CK2ß followed by protein A agarose. The immunoprecipitates were analyzed by Western blot analysis using rabbit antiserum to CK2{alpha} or CD5 followed by peroxidase conjugated goat anti-rabbit IgG and SuperSignal (Pierce, Rockford, IL) chemiluminescence substrate. The splenocyte population contained ~65% T cells, 45% B cells, and 3% CD5+ B cells as determined by flow cytometry analysis of cells following immunofluorescent staining with Abs to CD3, CD19, or CD5.

In vitro kinase assay

CK2 activity in immunoprecipitates was determined as described (10). In some experiments, heparin (Sigma, St. Louis, MO) was added to the kinase reaction at a final concentration of 10 µg/ml.


   Results and Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
References
 
CD5 cross-linking modulates cytosolic CK2 activity

Cross-linking of CD5 leads to the specific activation of CD5-associated CK2 (10). To determine whether CD5 ligation also regulates cytosolic CK2 activity, CH12 cells and Jurkat cells were stimulated with anti-CD5 or control Ab, and the CK2 activity in anti-CK2ß immunoprecipitates was determined to the standard CK2 substrate, RRREEETEEE (17). The concentration of Ab used to immunoprecipitate CK2 from cell lysates was limiting, and therefore the anti-CK2ß immunoprecipitates contained only a fraction of the total CK2. Basal CK2 activity in anti-CK2ß immunoprecipitates from unstimulated cells was greatly enhanced following CD5 stimulation (Fig. 1GoA). This increase represented activation since the amount of CK2 in anti-CK2ß immunoprecipitates from both stimulated and unstimulated cells was the same (Fig. 1GoB). The absence of detectable CD5 in the anti-CK2ß immunoprecipitates excludes the possibility that the observed activation was due to the presence of CD5-associated CK2 (Fig. 1GoC and data not shown). These results therefore show that CD5 stimulation leads to activation of cytosolic CK2 in addition to activation of CD5 associated CK2 (Ref. 10 and Fig. 6Go).



View larger version (38K):
[in this window]
[in a new window]
  		FIGURE 1. Cross-linking of CD5 activates cytosolic CK2 in cell lines. A, CK2 activity to CK2 standard peptide in anti-CK2ß immunoprecipitates from Jurkat and CH12 cells stimulated with anti-CD5 mAb or control Ab. B, Western blot of CK2{alpha} in anti-CK2ß immunoprecipitates from CD5 stimulated and unstimulated Jurkat and CH12 cells showing equivalent amounts of CK2. C, Western blot of CD5 and CK2{alpha} in anti-CD5 and anti-CK2ß immunoprecipitates from CD5-stimulated and unstimulated CH12 cells showing the absence of detectable CD5 in anti-CK2ß immunoprecipitates.

 


View larger version (40K):
[in this window]
[in a new window]
  		FIGURE 6. CD5-activation-dependent CK2 phosphorylation of CD5. Top, In vitro kinase assay and SDS-PAGE analysis of 32P incorporation in CD5 in anti-CD5 immunoprecipitates from CH12 cells stimulated with anti-CD5 or control Ab in the presence or absence of CK2 inhibitor, heparin. Bottom, In vitro kinase assay to CK2 standard peptide.

 
To test the possibility that the activation of cytosolic CK2 by CD5 may be associated with differential CD5-dependent modulation of TCR-mediated signaling in immature and mature T cells, we assessed the CK2 activity in anti-CK2ß immunoprecipitates of lysates prepared from thymocytes and splenocytes. Basal CK2 activity was lower in normal cells (Figs. 1GoA and 2), consistent with the hypothesis that the higher basal CK2 activity in transformed cells may promote unregulated growth and tumorigenicity (11, 18). In contrast to cell lines, however, CD5 cross-linking led to more than 50% inhibition of cytosolic CK2 activity in both thymocytes and splenocytes (Fig. 2Go). Although the mechanism for this effect is not known, the state of the cell appears to influence the CD5-dependent activation of CK2. The dichotomy in the effects of CD5 signaling on cytosolic CK2 activity in normal and transformed cells also suggested to us that the activation of cytosolic CK2 is independent of CD5-associated CK2. Of course, an alternate explanation is the activation of an inhibitor that acts on cytosolic CK2. Since it is the CD5+ B cell population that develop into B cell chronic lymphocytic leukemia (B-CLL) and other B cell malignancies and the level of CD5 expression in T cell leukemias is elevated, it would be of interest to determine whether the ability of CD5 to activate CK2 participates in the transformation process.



View larger version (11K):
[in this window]
[in a new window]
  		FIGURE 2. Cross-linking of CD5 inhibits cytosolic CK2 activity in thymocytes and splenocytes. CK2 activity to CK2 standard peptide in anti-CK2ß immunoprecipitates from cells stimulated with anti-CD5 or control Ab.

 
CD5-dependent regulation of CD5-associated CK2 in immature and mature T cells

The consistent inhibition of cytosolic CK2 activity in both thymocytes and splenocytes indicates that the differential role of CD5 signaling in immature and mature T cells cannot be explained by CD5-dependent regulation of cytosolic CK2 activity. Therefore, we tested the possibility that the differential role of CD5 may be associated with CD5-associated CK2 activity. No basal CD5-associated CK2 activity was seen in thymocytes or splenocytes treated with control Ab (Fig. 3Go). CD5 cross-linking in thymocytes led to greatly enhanced CD5-associated CK2 activity, but in marked contrast, splenic CD5 associated CK2 activity remained at basal level.



View larger version (21K):
[in this window]
[in a new window]
  		FIGURE 3. Effect of CD5 cross-linking on CD5-associated CK2 activity in thymocytes and splenocytes. CK2 activity to CK2 standard peptide in anti-CD5 or control Ab immunoprecipitates from cells stimulated with anti-CD5 or control Ab.

 
T cell number in both thymocyte and splenocyte preparations were similar (see Materials and Methods). To compare the dose-response of anti-CD5 stimulation necessary to activate CD5-associated CK2 activity in thymic and splenic T cells, a range of anti-CD5 mAb concentrations was used. We found that the activity of CD5-associated CK2 activity in splenocytes remained at basal levels at all concentrations of stimulating Ab, ranging from subsaturating to supersaturating, whereas CD5-associated CK2 activity in thymocytes exhibited a dose-dependent increase (Fig. 4GoA). Since splenic T cells express higher levels of CD5 than thymocytes, the lack of activation of CD5-associated CK2 in splenocytes is not a function of expression levels. The differential regulation of CD5-associated CK2 in immature and mature T cells is apparent over a broad range of stimulus intensity and may explain the opposite effects of CD5-mediated signaling in mature and immature T cells.



View larger version (24K):
[in this window]
[in a new window]
  		FIGURE 4. Effect of varying anti-CD5 concentrations and CD3 stimulation on CD5-associated CK2 activity. A, CK2 activity in thymocytes and splenocytes following stimulation with varying concentrations of anti-CD5. B, Thymic and splenic CK2 activity following stimulation of CD3 or costimulation of CD5 and CD3.

 
CD3 ligation/coligation does not activate CD5-associated CK2

The physical and functional association of CD5 with the TCR/CD3 complex raises the possibility that CD3 ligation/coligation may modify the of CD5-dependent activation of CK2. To test the role of CD3 ligation on CD5-associated CK2 activity we determined the CD5-associated CK2 activity in thymocytes and splenocytes following stimulation via CD3 and costimulation via both CD5 and CD3. Consistent with our previous study in Jurkat cells (10), CD5 but not CD3 stimulation activated CD5-associated CK2 activity in thymocytes, and this enhanced activity was not altered in cells stimulated simultaneously with anti-CD3 (Fig. 4GoB). The CD5-associated CK2 activity in splenocytes was not activated by either CD5 or CD3 stimulation nor was it activated by costimulation of CD5 andCD3. These data indicate that the activation of CK2 by CD5 is independent of TCR/CD3 signaling.

CD5 is a target of CD5-activated CK2-dependent phosphorylation

The dissociation of the activation of CD5-associated and cytosolic CK2 in normal T cells suggests that activated cytosolic CK2 is not derived from the CD5-associated pool. Therefore, we propose a model in which CD5 provides activated CK2 to the CD5-TCR/CD3 complex. Targets of activated CD5-associated CK2 are likely to be proximal signaling elements including CD5 itself, the members of TCR/CD3 complex, and signaling proteins associated with CD5 and TCR/CD3. Consistent with this hypothesis consensus sites for CK2-dependent phosphorylation are found in CD5, p56lck, p59fyn, vav, Zap70, p85-PI3 kinase, and PLC-{gamma}1, but not in CD3{epsilon} or {zeta}.

To demonstrate that endogenous CD5 is a target for CD5-dependent CK2 activation, CH12 cells were stimulated with anti-CD5 or treated with control Ab and immunoprecipitated with anti-CD5 or control Ab. The immunoprecipitates were incubated with [{gamma}-32P]ATP in an in vitro kinase assay, separated by SDS-PAGE, transferred to a polyvinylidene difluoride membrane and the membrane, was assayed first by autoradiography and then by anti-CD5 Western blot analysis. The heavily phosphorylated 67-kDa protein seen in anti-CD5 immunoprecipitates from CD5-stimulated cells was confirmed to be CD5 by anti-CD5 Western blot analysis and the amount was similar in stimulated and unstimulated cells (Fig. 5Go). The phosphorylation of CD5 was almost completely inhibited by the addition of 5 µg of the 16-amino acid synthetic C-terminal CD5 peptide (456-DNSSDSDYDLHGAQRL-471) that contains the CK2ß binding region Ser458-Ser461 in the cytoplasmic domain. A slightly smaller nonspecific phosphorylated protein was seen in all lanes.



View larger version (49K):
[in this window]
[in a new window]
  		FIGURE 5. Anti-CD5 induces phosphorylation of C terminus of CD5. In vitro kinase assay and SDS-PAGE analysis of 32P incorporation in CD5 in anti-CD5 immunoprecipitates from CH12 cells stimulated with anti-CD5 or control Ab, in the presence or absence of 456–471 CD5-derived peptide. The gel was transferred to polyvinylidene difluoride membrane and subjected to autoradiography followed by Western blot analysis with anti-CD5 antiserum.

 
Although CD5 stimulation reportedly results only in serine phosphorylation of its cytoplasmic domain (14), it is possible that the phosphorylation in Fig. 5Go reflects tyrosine phosphorylation on Tyr463 which lies within the CK2 binding motif (19, 20). To determine whether the CD5-induced phosphorylation is CK2-activation dependent, the phosphorylation of CD5 in anti-CD5 immunoprecipitates was examined by in vitro kinase assay in the presence or absence of heparin, a specific inhibitor of CK2 (16, 21, 22). The phosphorylation of CD5 from CD5-stimulated cells was completely inhibited in the presence of heparin and was associated with abrogation of activation of CD5-associated CK2 activity to standard CK2 substrate peptide (Fig. 6Go). Taken together, these results suggest that CD5 regulates CK2 kinase activity and is itself a substrate for CD5-induced CK2-dependent phosphorylation. A similar relationship has been shown for CD5 and the src family tyrosine kinase, p56lck (9).

Based on our data that CD5 ligation activates CD5-associated CK2 and that CD5 is also a substrate for active CK2, we suggest that CD5 participates in at least two pathways involving serine phosphorylation, the first being the activation of CK2-dependent signal transduction pathways and the second being modulation of recruitment of other molecules. Consistent with this hypothesis, Simarro et al. (23) have recently shown that the distal cytoplasmic domain of CD5 is essential for the activation of PLC-{gamma} and TCR/CD3-dependent and -independent diacylglycerol production and that the phosphorylation of Ser459 and Ser461, the sites of CK2-dependent phosphorylation, is likely to be involved in this pathway.

The differential CD5-dependent regulation of CK2 in thymocytes and splenocytes provides the first key to explain CD5-mediated attenuation of TCR signaling in immature T cells and costimulation in mature T cells. CD5 signaling activates both tyrosine and serine/threonine phosphorylation-dependent pathways (2, 8, 14, 20, 23, 24). The cumulative data from several studies suggest that CD5-dependent tyrosine phosphorylation pathways are primarily costimulatory to TCR/CD3 signals and promote activation of cells. We propose that the role of CD5-activated CK2 is to attenuate TCR/CD3-CD5 proximal targets that are activated by tyrosine phosphorylation. In mature T cells, an as yet unidentified modulator of CK2 activation alters the ability of CK2 to be activated and allows unopposed tyrosine phosphorylation dependent costimulation of TCR/CD3 signals. The model is testable in mice expressing altered CD5 that is deficient in its ability to regulate CK2.


   Acknowledgments
 
We thank Ms. Jessy Deshane for technical assistance.


   Footnotes
 
1 This work was supported in part by an Arthritis Investigator award by the Arthritis Foundation (to C.R.) and by Grant P60 A20614-22 from the National Institutes of Health (to R.P.K.). Back

2 Address correspondence and reprint requests to Dr. Chander Raman, Division of Clinical Immunology and Rheumatology, University of Alabama, LHRB 463, Birmingham, AL 35294-0007. E-mail address: Back

3 Abbreviations used in this paper: PLC, phospholipase C; CK2, casein kinase 2. Back

Received for publication May 8, 1998. Accepted for publication October 1, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 References
 

  1. Suzuki, H., Y. Shinkai, L. G. Granger, F. W. Alt, P. E. Love, A. Singer. 1997. Commitment of immature CD4+8+ thymocytes to the CD4 lineage requires CD3 signaling but does not require expression of clonotypic T cell receptor (TCR) chains. J. Exp. Med. 186:17.[Abstract/Free Full Text]
  2. Tarakhovsky, A., S. B. Kanner, J. Hombach, J. A. Ledbetter, W. Müller, N. Killeen, K. Rajewsky. 1995. A Role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 269:535.[Abstract/Free Full Text]
  3. Ceuppens, J. L., M. L. Baroja. 1986. Monoclonal antibodies to CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase bound OKT3. J. Immunol. 137:1816.[Abstract]
  4. June, C. H., P. S. Rabinovitch, J. A. Ledbetter. 1987. CD5 antibodies increase intracellular ionized calcium concentration in T cells. J. Immunol. 138:2782.[Abstract]
  5. Imboden, J. B., C. H. June, M. A. McCutcheon, J. A. Ledbetter. 1990. Stimulation of CD5 enhances signal transduction by the T-cell antigen receptor. J. Clin. Invest. 85:130.
  6. Vandenberghe, P., J. Verwilghen, F. Van Vaeck, J. L. Ceuppens. 1993. Ligation of the CD5 or CD28 molecules on resting human T cells induces expression of the early activation antigen CD69 by a calcium- and tyrosine kinase-dependent mechanism. Immunology 78:210.[Medline]
  7. Kroesen, B. J., A. Bakker, R. A. van Lier, H. T. The, L. de Leij. 1995. Bispecific antibody-mediated target cell-specific costimulation of resting T cells via CD5 and CD28. Cancer Res. 55:4409.[Abstract/Free Full Text]
  8. Burgess, K. E., M. Yamamoto, K. V. S. Prasad, C. E. Rudd. 1992. CD5 acts as a tyrosine kinase substrate within a receptor complex comprising T-cell receptor {zeta} chain/CD3 and protein-tyrosine kinases p56lck and p56fyn. Proc. Natl. Acad. Sci. USA 89:9311.[Abstract/Free Full Text]
  9. Raab, M., M. Yamamoto, C. E. Rudd. 1994. The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck. Mol. Cell. Biol. 14:2862.[Abstract/Free Full Text]
  10. Raman, C., A. Kuo, D. W. Litchfield, R. P. Kimberly. 1998. Regulation of casein kinase 2 by direct interaction with cell surface receptor CD5. J. Biol. Chem. 273:19183.[Abstract/Free Full Text]
  11. Allende, J. E., C. C. Allende. 1995. Protein kinases. IV. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J. 9:313.[Abstract/Free Full Text]
  12. Padmanabha, R., J. L. Chen-Wu, D. E. Hanna, C. V. Glover. 1990. Isolation, sequencing, and disruption of yeast CK{alpha}2 gene: casein kinase II is essential for viability of Saccharomyces cerevisiae. Mol. Cell. Biol. 10:4089.[Abstract/Free Full Text]
  13. Krek, W., G. Maridor, E. A. Nigg. 1992. Casein kinase II is a predominantly nuclear enzyme. J. Cell Biol. 116:43.[Abstract/Free Full Text]
  14. Alberola-Ila, J., L. Places, F. Lozano, J. Vives. 1993. Association of an activation inducible serine kinase activity with CD5. J. Immunol. 151:4423.[Abstract]
  15. Filhol, O., J. Baudier, C. Delphin, P. Loue-Mackenbach, E. M. Chambaz, C. Cochet. 1992. Casein kinase II and the tumor suppressor protein p53 associate in a molecular complex that is negatively regulated upon p53 phosphorylation. J. Biochem. 267:20577.
  16. Li, D. X., U. T. Meier, G. Dobrowolska, E. G. Krebs. 1997. Specific interaction between casein kinase 2 and the nucleolar protein Nopp140. J. Biochem. 272:3773.
  17. Kuenzel, E. A., E. G. Krebs. 1985. A synthetic substrate for casein kinase II. Proc. Natl. Acad. Sci. USA 82:737.[Abstract/Free Full Text]
  18. Litchfield, D. W., and B. Luscher. 1993. Casein kinase II in signal transduction and cell cycle regulation. Mol. Cell. Biochem. 127–128:187.
  19. Dennehy, K. M., R. Broszeit, D. Garnett, G. A. Durrhein, L. L. Spruyt, A. D. Beyers. 1997. Thymocyte activation induces the association of phosphatidylinositol 3-kinase and pp120 with CD5. Eur. J. Immunol. 27:679.[Medline]
  20. Gringhuis, S. I., L. F. M. H. de Leij, P. J. Coffer, E. Vellenga. 1998. Signaling through CD5 activates a pathway involving phosphatidylinositol 3-kinase, vav, and rac1 in human mature T lymphocytes. Mol. Cell. Biol. 18:1725.[Abstract/Free Full Text]
  21. Chen, J., L. A. Herzenberg, L. A. Herzenberg. 1991. Heparin alters the expression of different forms of immunoglobulin mu heavy chains and their associated proteins by pre-B cell lines and normal Ly-1 (CD5+) B cells. Int. Immunol. 3:1117.[Abstract/Free Full Text]
  22. Sarno, S., B. Boldyreff, O. Marin, B. Guerra, F. Meggio, O. G. Issinger, L. A. Pinna. 1995. Mapping the residues of protein kinase CK2 implicated in substrate recognition: mutagenesis of conserved basic residues in the {alpha}-subunit. Biochem. Biophys. Res. Commun. 206:171.[Medline]
  23. Simarro, M., C. Pelassy, J. Calvo, L. Places, C. Aussel, F. Lozano. 1997. The cytoplasmic domain of CD5 mediates both TCR/CD3-dependent and -independent diacylglycerol production. J. Immunol. 159:4307.[Abstract]
  24. Beyers, A. D., L. L. Spruyt, A. L. Williams. 1992. Molecular associations between T-lymphocyte antigen receptor complex and the surface antigen CD2, CD4, or CD8 and CD5. Proc. Natl. Acad. Sci. USA 89:2945.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
R. C. Axtell, L. Xu, S. R. Barnum, and C. Raman
CD5-CK2 Binding/Activation-Deficient Mice Are Resistant to Experimental Autoimmune Encephalomyelitis: Protection Is Associated with Diminished Populations of IL-17-Expressing T Cells in the Central Nervous System
J. Immunol., December 15, 2006; 177(12): 8542 - 8549.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
K. R. Ryan, D. McCue, and S. M. Anderton
Fas-mediated death and sensory adaptation limit the pathogenic potential of autoreactive T cells after strong antigenic stimulation
J. Leukoc. Biol., July 1, 2005; 78(1): 43 - 50.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. C. Axtell, M. S. Webb, S. R. Barnum, and C. Raman
Cutting Edge: Critical Role for CD5 in Experimental Autoimmune Encephalomyelitis: Inhibition of Engagement Reverses Disease in Mice
J. Immunol., September 1, 2004; 173(5): 2928 - 2932.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. M. Vila, J. Calvo, L. Places, O. Padilla, M. Arman, I. Gimferrer, C. Aussel, J. Vives, and F. Lozano
Role of Two Conserved Cytoplasmic Threonine Residues (T410 and T412) in CD5 Signaling
J. Immunol., January 1, 2001; 166(1): 396 - 402.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Pena-Rossi, L. A. Zuckerman, J. Strong, J. Kwan, W. Ferris, S. Chan, A. Tarakhovsky, A. D. Beyers, and N. Killeen
Negative Regulation of CD4 Lineage Development and Responses by CD5
J. Immunol., December 15, 1999; 163(12): 6494 - 6501.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. F. Cotlin, M. A. Siddiqui, F. Simpson, and J. F. Collawn
Casein Kinase II Activity Is Required for Transferrin Receptor Endocytosis
J. Biol. Chem., October 22, 1999; 274(43): 30550 - 30556.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Carmo, M. A. A. Castro, and F. A. Arosa
CD2 and CD3 Associate Independently with CD5 and Differentially Regulate Signaling Through CD5 in Jurkat T Cells
J. Immunol., October 15, 1999; 163(8): 4238 - 4245.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Raman, C.
Right arrow Articles by Kimberly, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Raman, C.
Right arrow Articles by Kimberly, R. P.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS