Signal Transduction Pathways Involved in B‐Cell Induction

Baixerás, Elena; Kroemer, Guido; Cuende, Eduardo; Márquez, Carlos; Boscá, Lisardo; Martinez, J.; Martı́nez-A, Carlos

doi:10.1111/j.1600-065x.1993.tb00836.x

Cited by 41 publications

(18 citation statements)

References 214 publications

(121 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of these receptors lack an intrinsic tyrosine kinase activity. Therefore, they recruit and activate cytoplasmic tyrosine kinases, such as Src, Syk, Zap-70, and Jak tyrosine kinases (27,(45)(46)(47)(48)(49). Thus, our next goal was to investigate which of the two IL-15R chains expressed by Raji cells (␣ or ␥) is capable of signaling upon IL-15 stimulation, which tyrosine kinases are activated, and with which of the two IL-15R chains selected tyrosine kinases associate.…”

Section: Syk Physically Associates With the Il-15r␣ Chain After Il-15mentioning

confidence: 99%

The IL-15Rα Chain Signals Through Association with Syk in Human B Cells

Bulanova

Budagian

Pohl

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

The α-chain of the IL-15R (IL-15Rα) serves as the specific, high-affinity receptor for IL-15. It is expressed by lymphoid and nonlymphoid cells, including B cell lymphoma lines. In this study, we have further explored IL-15Rα-mediated signaling in activated primary B cells and in Raji cells, a human B-lymphoblastoid cell line which expresses the IL-15Rα and IL-2Rγ chains, but lacks the IL-2Rβ chain. Stimulation of Raji cells with IL-15 induces their proliferation and rescues them from C2-ceramide-induced apoptosis. By immunoprecipitation and Western blotting, we show that treatment of Raji cells and activated primary B cells with IL-15 induces coprecipitation of Syk kinase with the IL-15Rα chain. Upon association, the activated Syk kinase phosphorylates the IL-15Rα chain as well as phospholipase Cγ, which coprecipitates with Syk. Furthermore, transfection of Raji cells with stem-loop Syk antisense oligonucleotides prevents IL-15Rα and phospholipase Cγ phosphorylation as well as the inhibition of apoptosis by IL-15. Mutation of a defined region of the intracellular signaling portion of IL-15Rα (Tyr227) abrogates both the IL-15Rα/Syk association and IL-15Rα phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Rα chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells.

show abstract

Section: Syk Physically Associates With the Il-15r␣ Chain After Il-15mentioning

confidence: 99%

The IL-15Rα Chain Signals Through Association with Syk in Human B Cells

Bulanova

Budagian

Pohl

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…This Ca 2ϩ hump may be the result of store-operated Ca 2ϩ entry as described below. These results suggest that mouse myeloid DC predominantly express metabotropic purinoceptors, which mobilize Ca 2ϩ by formation of IP 3 and not via plasma membrane ATP-gated ion channels. This is consistent with the recent report of functional P2Y type receptors in human myeloid DC (25).…”

Section: Absence Of Voltage- Atp- or Dhp-activated Ca 2ϩ Entrymentioning

confidence: 85%

“…Ca 2ϩ signaling in DC represents one such area, despite the fact that alterations in intracellular Ca 2ϩ are known to underlie many immune responses. Indeed, a sustained increase in intracellular Ca 2ϩ accompanies T and B cell receptor signaling and is necessary for gene activation, cellular proliferation, and Ab secretion (3,4).…”

Section: A Lthough Dendritic Cells (Dc)mentioning

confidence: 99%

See 1 more Smart Citation

Fundamental Ca2+ Signaling Mechanisms in Mouse Dendritic Cells: CRAC Is the Major Ca2+ Entry Pathway

Hsu

O’Connell

Klyachko

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

Although Ca2+-signaling processes are thought to underlie many dendritic cell (DC) functions, the Ca2+ entry pathways are unknown. Therefore, we investigated Ca2+-signaling in mouse myeloid DC using Ca2+ imaging and electrophysiological techniques. Neither Ca2+ currents nor changes in intracellular Ca2+ were detected following membrane depolarization, ruling out the presence of functional voltage-dependent Ca2+ channels. ATP, a purinergic receptor ligand, and 1–4 dihydropyridines, previously suggested to activate a plasma membrane Ca2+ channel in human myeloid DC, both elicited Ca2+ rises in murine DC. However, in this study these responses were found to be due to mobilization from intracellular stores rather than by Ca2+ entry. In contrast, Ca2+ influx was activated by depletion of intracellular Ca2+ stores with thapsigargin, or inositol trisphosphate. This Ca2+ influx was enhanced by membrane hyperpolarization, inhibited by SKF 96365, and exhibited a cation permeability similar to the Ca2+ release-activated Ca2+ channel (CRAC) found in T lymphocytes. Furthermore, ATP, a putative DC chemotactic and maturation factor, induced a delayed Ca2+ entry with a voltage dependence similar to CRAC. Moreover, the level of phenotypic DC maturation was correlated with the extracellular Ca2+ concentration and enhanced by thapsigargin treatment. These results suggest that CRAC is a major pathway for Ca2+ entry in mouse myeloid DC and support the proposal that CRAC participates in DC maturation and migration.

show abstract

“…A sustained increase in free cytosolic Ca 2þ accompanies T and B cell receptor signalling and is necessary for interleukin-2 production, cellular proliferation and antibody secretion. (64,65) Similarly, many critical processes and functions in DCs appear to involve Ca 2þ signalling.…”

Section: Dendritic Cell (Dc) Functionmentioning

confidence: 99%

The IRBIT domain adds new functions to the AHCY family

2008

View full text Add to dashboard Cite

SummaryDuring the past few years, the IRBIT domain has emerged as an important add-on of S-adenosyl-L-homocystein hydrolase (AHCY), thereby creating the new family of AHCY-like proteins. In this review, we discuss the currently available data on this new family of proteins. We describe the IRBIT domain as a unique part of these proteins and give an overview of its regulation via (de)phosphorylation and proteolysis. The second part of this review is focused on the potential functions of the AHCY-like proteins. We propose that the IRBIT domain serves as an anchor for targeting AHCY-like proteins towards cytoplasmic targets. This leads to regulation of (i) The AHCY family AHCY S-adenosyl-L-homocystein (SAH) hydrolase (AHCY) is a ubiquitous, tetrameric enzyme that catalyzes the reversible hydrolysis of SAH to adenosine and L-homocysteine. SAH is formed as a by-product of S-adenosyl-L-methionine (SAM) through transmethylation reactions. The hydrolysis of SAH is required to maintain low cellular concentrations of SAH, which is a product inhibitor of S-adenosyl-L-methionine (SAM)-dependent transmethylation reactions.(1-4) Inhibition of AHCY results in the intracellular accumulation of SAH, causing a significant increase in the intracellular SAH/SAM ratio and the subsequent inhibition of SAM-dependent methylations.( 5 -8) SAM is the major methyl donor for delivery of methyl groups to DNA, RNA, proteins and cellular metabolites in eukaryotes and SAH hydrolysis is the only source of homocysteine in mammals.(9) AHCY has become an attractive target for design of broad-spectrum antiviral agents because of the inhibitory effects of elevated intracellular SAH concentrations on viral mRNA cap-methylating enzymes. (10,11) In addition to these antiviral effects, AHCY inhibitors have also been attributed antiparasitic, (12,13) anti-arthritic (14) and immunosuppressive (15) effects.The importance of AHCY for mammalian survival is suggested by the fact that a chromosomal deletion that includes the gene encoding AHCY causes embryonic lethality in mice.(16) Elevated homocysteine levels have been reported as a risk factor for dementia and Alzheimer's disease, (17) and as a possible risk marker for vascular disease. (18,19) Human AHCY deficiency, such as in hypermethionemia, results in severe biochemical abnormalities, including plasma elevations of 150-fold in SAH, 30-fold in SAM and 12-fold in methionine. (20,21) So far, three mutations in the AHCY gene have been found to reduce the activity of the AHCY enzyme, resulting in the signs and symptoms of hypermethionemia. (22,23) AHCY orthologues have been identified in many species, including bacteria, nematodes, yeast, plants, insects and vertebrates. In contrast, the AHCY-like (AHCYL) family members AHCYL1 (also termed IRBIT, the inositol 1,4, 5-trisphosphate (IP 3 ) receptor (IP 3 R) binding protein released by IP 3 ) and AHCYL2 (KIAA0828 in human) are only predicted in segmented multicellular organisms, like vertebrates (eg Takifugu rubripes (fugu fish), Danio rerio (zebrafish), Xen...

show abstract

Signal Transduction Pathways Involved in B‐Cell Induction

Cited by 41 publications

References 214 publications

The IL-15Rα Chain Signals Through Association with Syk in Human B Cells

The IL-15Rα Chain Signals Through Association with Syk in Human B Cells

Fundamental Ca2+ Signaling Mechanisms in Mouse Dendritic Cells: CRAC Is the Major Ca2+ Entry Pathway

The IRBIT domain adds new functions to the AHCY family

Contact Info

Product

Resources

About