CoChat
Sign Up
Cited by 54Protein Kinase Regulation and GTPase SignalingT-cell and B-cell ImmunologySignaling Pathways in Disease

CD38 Signaling Regulates B Lymphocyte Activation via a Phospholipase C (PLC)-γ2-Independent, Protein Kinase C, Phosphatidylcholine-PLC, and Phospholipase D-Dependent Signaling Cascade

Moreno-García, Miguel E, López-Bojórques, Lucia N, Zentella, Alejandro, Humphries, Lisa A, Rawlings, David J, Santos-Argumedo, Leopoldo·2005·The Journal of Immunology
DOI 10.4049/jimmunol.174.5.2687
Open this paper in CoChat — free account

Abstract

The CD38 cell surface receptor is a potent activator for splenic, B lymphocytes. The molecular mechanisms regulating this response, however, remain incompletely characterized. Activation of the nonreceptor tyrosine kinase, Btk, is essential for CD38 downstream signaling function. The major Btk-dependent substrate in B cells, phospholipase C-gamma2 (PLC-gamma2), functions to generate the key secondary messengers, inositol-1,4,5 trisphosphate and diacylglycerol. Surprisingly, CD38 ligation results in no detectable increase in phosphoinositide metabolism and only a minimal increase in cytosolic calcium. We hypothesized that Btk functioned independently of PLC-gamma2 in the CD38 signaling pathway. Accordingly, we demonstrate that CD38 cross-linking does not result in the functional phosphorylation of PLC-gamma2 nor an increase in inositol-1,4,5 trisphosphate production. Furthermore, splenic B cells exhibit a normal CD38-mediated, proliferative response in the presence of the phosphoinositide-PLC inhibitor, U73122. Conversely, protein kinase C (PKC) beta-deficient mice, or PKC inhibitors, indicated the requirement for diacylglycerol-dependent PKC isoforms in this pathway. Loss of PKC activity blocked CD38-dependent, B cell proliferation, NF-kappaB activation, and subsequent expression of cyclin-D2. These results suggested that an alternate diacylglycerol-producing phospholipase must participate in CD38 signaling. Consistent with this idea, CD38 increased the enzymatic activity of…

Integrity signals

Registry

Crossref · 10.4049/jimmunol.174.5.2687

Cites

67 of 67 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PLCγ2 activation results in activation of phospholipase D and cell spreading, and brings on Erk signaling.

    “In addition to the production of IP3, DAG, and calcium flux, PLCγ2 activation results in activation of phospholipase D and cell spreading (12, 13, 14, 15, 16, 17), bringing on other vital cell signaling processes such as Erk (18).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [16]

  • Alternative signaling pathways through CD38, CD40, IL-4R, LPS/TLR4/MyD88, and CD86 also utilize PLCγ2, while TGF-βR stimulation inhibits PLCγ2 function in B cells.

    “Aside from BCR engagement, there are alternative signaling pathways initiated through extracellular immunological receptors that also utilize PLCγ2 to function, which include CD38 (16), CD40 (52), IL-4R (53, 54, 55) and the LPS/TLR4/MyD88 pathway, the latter of which induces ERK and NK-κB phosphorylation in MEKs in a PI3K-independent fashion (56). CD86 engagement was also observed to signal via PL”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [16]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Moreno-García, M. E., López-Bojórques, L. N., Zentella, A., Humphries, L. A., Rawlings, D. J., & Santos-Argumedo, L.
Affiliations
  • Departments of Cell Biology , Mexico D.F.
  • Department of Cell Biology, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México , Mexico D.F. ,
  • University of Washington (US)
  • Molecular Biomedicine, Centro de Investigación y Estudios Avanzados , Mexico D.F.
ORCID
Rawlings, David J
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2005-03-01
Volume
174
Issue
5
Pages
2687-2695
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.174.5.2687
OpenAlex
W1499772026
Cited by
54
References
67
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 2 · 2012: 2
FWCI
2.14
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (2r01ai033617-04)
  • National Cancer Institute (R01CA081140, CA 81140)
  • National Institute of Allergy and Infectious Diseases (AI-38348, R01AI038348, AI33617)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD37091, R01HD037091)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
CD38, B cell activation, Bruton's tyrosine kinase, protein kinase C beta, phospholipase D, diacylglycerol, phosphoinositide metabolism, NF-κB activation, cyclin D2, B cell proliferation, U73122, D609
MeSH terms
Animals, B-Lymphocytes, Bridged-Ring Compounds, Diglycerides, Enzyme Activation, Enzyme Induction, Female, Isoenzymes, Lymphocyte Activation, Membrane Glycoproteins, Mice, Inbred BALB C, Norbornanes, Type C Phospholipases, Phospholipase D, Protein Kinase C, Spleen, Thiocarbamates, Thiones, Signal Transduction, Antigens, CD, Cyclins, NF-kappa B, Mice, Knockout, ADP-ribosyl Cyclase, Cell Proliferation, Mice, Phospholipase C gamma, ADP-ribosyl Cyclase 1, Cyclin D2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review