Cited by 199Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesNF-κB Signaling Pathways

Involvement of Guanosine Triphosphatases and Phospholipase C-γ2 in Extracellular Signal–regulated Kinase, c-Jun NH2-terminal Kinase, and p38 Mitogen-activated Protein Kinase Activation by the B Cell Antigen Receptor

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Hashimoto, Ari, Okada, Hidetaka, Jiang, Aimin, Kurosaki, Mari, Greenberg, Steven, Clark, Edward A., Kurosaki, Tomohiro·1998·The Journal of Experimental Medicine

Abstract

Mitogen-activated protein (MAP) kinase family members, including extracellular signal–regulated kinase (ERK), c-Jun NH2-terminal kinase ( JNK), and p38 MAP kinase, have been implicated in coupling the B cell antigen receptor (BCR) to transcriptional responses. However, the mechanisms that lead to the activation of these MAP kinase family members have been poorly elucidated. Here we demonstrate that the BCR-induced ERK activation is reduced by loss of Grb2 or expression of a dominant-negative form of Ras, RasN17, whereas this response is not affected by loss of Shc. The inhibition of the ERK response was also observed in phospholipase C (PLC)-γ2–deficient DT40 B cells, and expression of RasN17 in the PLC-γ2–deficient cells completely abrogated the ERK activation. The PLC-γ2 dependency of ERK activation was most likely due to protein kinase C (PKC) activation rather than calcium mobilization, since loss of inositol 1,4,5-trisphosphate receptors did not affect ERK activation. Similar to cooperation of Ras with PKC activation in ERK response, both PLC-γ2–dependent signal and GTPase are required for BCR-induced JNK and p38 responses. JNK response is dependent on Rac1 and calcium mobilization, whereas p38 response requires Rac1 and PKC activation.

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  • 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).”

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Research works printed but not linked: 3

  1. [23]Teramoto H Salem P Robbins KC Bustelo XR Gutkind JS Tyrosine phosphorylation of the vavproto-oncogene products links FcεRI to the Rac1-JNK pathway J Biol Chem 1997 272 10751 10755 9099726
  2. [44]Zhang W Sloan-Lancaster J Kitchen J Trible RP Samelson LE LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation Cell 1998 92 83 92 9489702
  3. [63]Maeda A Kurosaki M Ono M Takai T Kurosaki T Requirement of tyrosine phosphatase SHP-1 and SHP-2 for PIR-B–mediated inhibitory signal J Exp Med 1998 187 1355 1360 9547347 PMC2212224

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Authors
Hashimoto, A., Okada, H., Jiang, A., Kurosaki, M., Greenberg, S., Clark, E. A., & Kurosaki, T.
Affiliations
Kansai Medical University (JP)
Corresponding author
Kurosaki, Tomohiro
Venue
The Journal of Experimental Medicine
Published
1998-10-05
Volume
188
Issue
7
Pages
1287-1295
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W1965678722
Cited by
199
References
68
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 8 · 2014: 6 · 2013: 5 · 2012: 2
FWCI
5.59
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p01gm042508-09)
  • National Institute of General Medical Sciences (GM42508, GM-37905, R01GM037905)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
B cell receptor, extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, p38 MAPK, PLCγ2, Ras, Grb2, Shc, protein kinase C, Rac1, calcium mobilization, IP3 receptor, MAPK activation, signal transduction, B cell signaling
MeSH terms
Animals, Cell Line, Chickens, Enzyme Activation, Isoenzymes, Type C Phospholipases, Protein Kinase C, Proteins, Receptors, Antigen, B-Cell, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, GTP-Binding Proteins, Mitogen-Activated Protein Kinase 1, GTP Phosphohydrolases, rac GTP-Binding Proteins, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, GRB2 Adaptor Protein, Phospholipase C gamma

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