Phospholipase Cβ Is Critical for T Cell Chemotaxis

Bach, Tami L; Chen, Qing-Min; Kerr, Wesley T; Wang, Yanfeng; Lian, Lurong; Choi, John K; Wu, Dianqing; Kazanietz, Marcelo G; Koretzky, Gary A; Zigmond, Sally; Abrams, Charles S

doi:10.4049/jimmunol.179.4.2223

Cited by 68Chemokine receptors and signalingProtein Kinase Regulation and GTPase SignalingSphingolipid Metabolism and Signaling

Phospholipase Cβ Is Critical for T Cell Chemotaxis

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Bach, Tami L, Chen, Qing-Min, Kerr, Wesley T, Wang, Yanfeng, Lian, Lurong, Choi, John K, Wu, Dianqing, Kazanietz, Marcelo G +3 more·2007·The Journal of Immunology

DOI 10.4049/jimmunol.179.4.2223PMC PMC3228861

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Abstract

Chemokines acting through G protein-coupled receptors play an essential role in the immune response. PI3K and phospholipase C (PLC) are distinct signaling molecules that have been proposed in the regulation of chemokine-mediated cell migration. Studies with knockout mice have demonstrated a critical role for PI3K in Gαi protein-coupled receptor-mediated neutrophil and lymphocyte chemotaxis. Although PLCβ is not essential for the chemotactic response of neutrophils, its role in lymphocyte migration has not been clearly defined. We compared the chemotactic response of peripheral T cells derived from wild-type mice with mice containing loss-of-function mutations in both of the two predominant lymphocyte PLCβ isoforms (PLCβ2 and PLCβ3), and demonstrate that loss of PLCβ2 and PLCβ3 significantly impaired T cell migration. Because second messengers generated by PLCβ lead to a rise in intracellular calcium and activation of PKC, we analyzed which of these responses was critical for the PLCβ-mediated chemotaxis. Intracellular calcium chelation decreased the chemotactic response of wild-type lymphocytes, but pharmacologic inhibition of several PKC isoforms had no effect. Furthermore, calcium efflux induced by stromal cell-derived factor-1α was undetectable in PLCβ2β3-null lymphocytes, suggesting that the migration defect is due to the impaired ability to increase intracellular calcium. This study demonstrates that, in contrast to neutrophils, phospholipid second messengers generated by PLCβ play a critical role in T lymphocyte chemotaxis.

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Among the 30 enriched terms, two GO-terms are T-cell chemotaxis and cell-cell adhesion which play a critical role in the immune system.
“Interestingly, among the 30 enriched terms, two GO-terms are T-cell chemotaxis and cell–cell adhesion which play a critical role in the immune system (Springer, 1990; Gerard and Rollins, 2001; Bach et al., 2007).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Bach et al., 2007

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“…by iHS, CLR, and Rsb. Frontiers in Genetics | www.frontiersin.org November 2019 | Volume 10 | Article 1095 enriched terms, two GO-terms are T-cell chemotaxis and cell– cell adhesion which play a critical role in the immune system (Springer, 1990; Gerard and Rollins, 2001; Bach et al., 2007).”
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Authors: Bach, T. L., Chen, Q.-M., Kerr, W. T., Wang, Y., Lian, L., Choi, J. K., Wu, D., Kazanietz, M. G., Koretzky, G. A., Zigmond, S., & Abrams, C. S.
Affiliations: Department of Medicine , Philadelphia, PA 19104
Children's Hospital of Philadelphia (US)
UConn Health (US)
Department of Pharmacology , Philadelphia, PA 19104
Abramson Cancer Center (US)
University of Pennsylvania (US)
ORCID: Kerr, Wesley T
Wang, Yanfeng
Choi, John K
Kazanietz, Marcelo G
Koretzky, Gary A
Abrams, Charles S
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2007-08
Volume: 179
Issue: 4
Pages: 2223-2227
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.179.4.2223
PMC: PMC3228861
OpenAlex: W2163771546
Cited by: 68
References: 49
Citations by year: 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 5
FWCI: 3.04
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL080706)
National Cancer Institute (P01CA093615)
National Institute of General Medical Sciences (R01GM054597)
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords: phospholipase C beta, PLCβ2, PLCβ3, T cell chemotaxis, lymphocyte migration, chemokine signaling, G protein-coupled receptors, intracellular calcium, stromal cell-derived factor-1α, phosphatidylinositol 3-kinase, protein kinase C, calcium chelation, knockout mice
MeSH terms: Animals, Chemotaxis, Isoenzymes, Mutation, Neutrophils, Type C Phospholipases, T-Lymphocytes, Mice, Knockout, Chemokines, GTP-Binding Protein alpha Subunits, Gi-Go, Receptors, Chemokine, Chemokines, CXC, Phosphatidylinositol 3-Kinases, Calcium Signaling, Mice, Chemokine CXCL12, Phospholipase C beta

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Phospholipase Cβ Is Critical for T Cell Chemotaxis

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