Isoform‐specific associations of CD45 with accessory molecules in human T lymphocytes

Dianzani, Umberto; Redoglia, Valter; Malavasi, Fabio; Bragardo, Manuela; Pileri, Alessandro; Janeway, Charles A.; Bottomly, Kim

doi:10.1002/eji.1830220212

Cited by 86 publications

(41 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results suggest that the CD45 PTPase is responsible for the C chain dephosphorylation. Thus, the CD45 PTPase may have two roles in T-cell activation, (i) the established role in initiation of activation via dephosphorylation of the Lck and/or Fyn tyrosine kinases and (ii) a second role in the termination of the response via dephosphorylation of C. It is possible that different CD45 isoforms, by differentially associating with CD4, CD8, and the TCR-CD3 complex, affect both the threshold and duration ofT-cell activation (48,49).…”

Section: Resultsmentioning

confidence: 99%

Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain.

Furukawa

Itoh

Krueger

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

155

120

View full text Add to dashboard Cite

The CD45 transmembrane protein-tyrosine phosphatase (PTPase, EC 3.1.3.48) plays an essential role in T-cell activation by activating the Lck and/or Fyn proteintyrine kinases. However, numerous experiments have indicated that CD45 may have both mulatory and inhibitory roles in T-cell activation. Thus, it is unlikely that the two kinases are the sole substrates of the CD45 PTPase. Furthermore, the complex regulation of the alternative splicing of the extracellular domain in various leukocyte lineages also suggests additional roles for the CD45 PTPase. To identify such functions, it is necessary to identify physiologically relevant substrates of the CD45 PTPase other than the two protein-tyrosine kinases. To this end, we searched for high-affinity substrates of the CD45 VPTase among the tyrosine-phosphorylated T-cell proteins by using purified glutathione S-transferase-CD45 fusion molecules. The enzymatically inactive CD45 C828S mutant protein, in which the cysteine residue at the catalytic center was changed to a serine residue, bound tightly to the phosphorylated CD3 gchailn. This binding was specific to CD45 PTPase, as neither the leukocyte common antigen-related molecule (LAR) PTPase nor the CD45-LAR hybrid PTPases bound the phosphorylated CD3 S chain. Furthermore, phosphorylated CD3 C chain was preferentially dephosphorylated by the wild-type CD45 PTPase under conditions that did not significantly dephosphorylate other cellular proteins. Thus, the phosphorylated CD3 S chain is a specific and high-affinity substrate of the CD45 PTPase. These results suggest that CD45 is involved in the termination of the T-cell response via dephosphorylation of CD3 S chain.

show abstract

Section: Resultsmentioning

confidence: 99%

Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain.

Furukawa

Itoh

Krueger

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

155

120

View full text Add to dashboard Cite

show abstract

“…Antibodies against RB have been shown to have both an immunosuppressive [37][38][39] and stimulatory 40,41 effect on lymphoid cell behavior depending on various environmental factors, including differential associations with multiple surface molecules. 42,43 Anti-RB treatment is useful as an immunotherapeutic agent and induces transplant tolerance. 39,[44][45][46][47] It must be stressed that B cells play a critical role in these processes.…”

Section: Discussionmentioning

confidence: 99%

Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression

Jackson

Harp

Patel

et al. 2009

Blood

View full text Add to dashboard Cite

We previously reported that RO ؉ expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD ؊ CD38 ؉ GC B cells, into different fractions based on RB expression. Although each subset contained RB ؉ cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB ؉ GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB-and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM ؉ IgD ؉ CD38 ؉ CD27 ؊ ) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgD ؊ CD38 ؉؉ CD27 ؉ ) and memory (IgD ؊ CD38 ؊ CD27 ؉ ) transition. Interestingly, RB ؉ GC B cells showed increased signs of terminal differentiation toward CD27 ؉ post-GC early plasmablast (increased CD38 and RO) or early memory IntroductionImmune function is uncompromisingly governed by at least 3 interdependent principles including recognition, effector function, and transition. Early naive B and T cells that successfully bind foreign antigen become activated and undergo developmental transition toward more mature, faster responding memory subsets. In contrast, lymphocytes that bind self-antigen in the periphery are usually counterselected against and undergo a different type of transition, one toward apoptosis or anergy. Ineffectual negative selection against self-specific B cells has been associated with the development of autoimmune and neoplastic diseases. Unfortunately, potential factors responsible for the redirection or abrogation of transitions toward cell death and anergy have not been conclusively determined. Antibody sequence analyses revealed that B cells participating in autoreactive responses are often mutated and show signs of selection for self-antigen. 1,2 This suggests that somatic hypermutation (SHM) during proliferation and activationbased transitions in the dynamic germinal center reaction may play a role (whether direct or indirect) in disease pathogenesis.We therefore sought to develop an expedient approach that would allow for the reproducible identification of B-cell populations that exist at different transitional stages based on their states of activation, SHM-dependent diversification, and developmental progression toward adjacent downstream subsets. Delineating how surface marker profiles change as B cells transition between key stages (especially when immunoregulatory markers such as CD45 protein tyrosine phosphatase are included in such profiles) should increase our understanding of B-cell development and ultimately how to circumvent dysregulated processes that could lead to disease.Over the past 3 decades, our research laboratory has investigated multiple aspects of human B-cell development and the molecular processes that collectively shape the peripheral BCR repertoi...

show abstract

“…The full-length and the various deleted forms of CD45-AP cDNA were then ligated to pGEX-1T expression vector downstream from GST, and recombinant GST fusion proteins were produced in E. coli. The recombinant proteins bound to equal amounts of glutathione-Sepharose 4B were incubated with lysates of YAC-1 cells metabolically labeled by 14 C-labeled amino acid incorporation. Material bound to the beads was analyzed by SDS-PAGE (Fig.…”

Section: Binding Of Various Deleted Forms Of In Vitro Translatedmentioning

confidence: 99%

“…Furthermore, CD45 is required for signal transduction pathways of monocytes (9), natural killer cells (10), and mast cells (11). Physical associations between CD45 and various membrane proteins involved in T cell activation, such as CD2 (12), CD4 (13,14), CD8 (13,14), Thy-1 (15), T cell receptor (14), CD26 (16), and LFA-1 (14), as well as components of the B cell antigen receptor complex (17), have been documented under certain circumstances. It is not clear how specifically these proteins interact with CD45 and what their binding sites are.…”

mentioning

confidence: 99%

Characterization of the Interaction between CD45 and CD45-AP

Kitamura

Maiti

et al. 1995

Journal of Biological Chemistry

View full text Add to dashboard Cite

CD45, a leukocyte-specific transmembrane protein tyrosine phosphatase, is required for critical signal transduction pathways in immune responses. To elucidate the molecular interactions of CD45 with other proteins involved in CD45-mediated signal transduction pathways, we have recently cloned a 30-kDa phosphorylated protein, CD45-AP, which specifically associates with CD45. Binding analysis employing several deleted or chimeric forms of CD45-AP and CD45 demonstrated that the potential transmembrane segment of CD45-AP bound to the transmembrane portion of CD45. CD45-AP was found in particulate fractions of lymphocytes along with CD45, indicating that it is likely to be a transmembrane protein. In addition, CD45-AP was resistant to proteolysis by tosylphenylalanyl chloromethyl ketonetreated trypsin applied to intact cells. This is consistent with the most likely membrane orientation of CD45-AP predicted from the amino acid sequence, that is, only a short amino-terminal segment of CD45-AP is extracellular. We propose that CD45-AP interacts with CD45 at the plasma membrane and that the bulk of CD45-AP located in the cytoplasm act as an adapter which directs the interaction between CD45 and other molecules involved in CD45-mediated signal transduction pathways.CD45 plays a critical role in signal transduction pathways essential for immune responses (1). The intracellular domain of CD45 exhibits protein tyrosine phosphatase activity (2) and differential usage of extracellular NH 2 -terminal exons results in several isotypes of CD45 which are variably expressed in a cell lineage-and developmental stage-specific manner (1, 3). It has been proposed that CD45 activates src family protein tyrosine kinases associated with the T cell receptor signaling complex, p56 lck (4, 5) and p59 fyn (6, 7), by dephosphorylating their down-regulatory tyrosyl residues. Thus, CD45 appears to be required at the onset of the T cell receptor-mediated signal transduction pathway. CD45 appears to play a similar role in B lymphocytes in combination with their src protein tyrosine kinases (8). Furthermore, CD45 is required for signal transduction pathways of monocytes (9), natural killer cells (10), and mast cells (11). Physical associations between CD45 and various membrane proteins involved in T cell activation, such as CD2 (12), CD4 (13, 14), CD8 (13, 14), Thy-1 (15), T cell receptor (14), CD26 (16), and LFA-1 (14), as well as components of the B cell antigen receptor complex (17), have been documented under certain circumstances. It is not clear how specifically these proteins interact with CD45 and what their binding sites are. A cytoskeletal protein, fodrin, has been reported to interact with the cytoplasmic portion of CD45 and stimulate its protein tyrosine phosphatase activity (18). In addition, CD45 has been reported to be one of surface glycoproteins to which CD22, the B lineage-specific cell surface glycoprotein and a sialic acidbinding lectin, binds (19).We have recently reported the molecular cloning of a novel 30-kDa phosphorylated ...

show abstract

Isoform‐specific associations of CD45 with accessory molecules in human T lymphocytes

Cited by 86 publications

References 41 publications

Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain.

Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain.

Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression

Characterization of the Interaction between CD45 and CD45-AP

Contact Info

Product

Resources

About