Activation of Phospholipase Cγ2 by Tyrosine Phosphorylation

Özdener, Fatih; Dangelmaier, Carol; Ashby, Barrie; Kunapuli, Satya P.; Daniel, James L.

doi:10.1124/mol.62.3.672

Cited by 61Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesPI3K/AKT/mTOR signaling in cancer

Activation of Phospholipase Cγ2 by Tyrosine Phosphorylation

Özdener, Fatih, Dangelmaier, Carol, Ashby, Barrie, Kunapuli, Satya P., Daniel, James L.·2002·Molecular Pharmacology

DOI 10.1124/mol.62.3.672

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Abstract

Phospholipase Cgamma2 (PLCgamma2) has been implicated in collagen-induced signal transduction in platelets and antigen-dependent signaling in B-lymphocytes. It has been suggested that tyrosine kinases activate PLCgamma2. We expressed the full-length cDNA for human PLCgamma2 in bacteria and purified the recombinant enzyme. The recombinant enzyme was Ca(2+)-dependent with optimal activity in the range of 1 to 10 microM Ca(2+). In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. Using site-directed mutagenesis, we investigated the role of specific tyrosine residues in activation of PLCgamma2. A mutant form of PLCgamma2, in which all three tyrosines at positions 743, 753, and 759 in the SH2-SH3 linker region were replaced by phenylalanines, exhibited decreased Lck-induced phosphorylation and completely abolished the Lck-dependent activation of PLCgamma2. Individual mutations of these tyrosine residues demonstrated that tyrosines 753 and 759, but not 743, were responsible for Lck-induced activation of PLCgamma2. To confirm these results, we procured a phosphospecific antibody to a peptide containing phosphorylated tyrosines corresponding to residues 753 and 759. This antibody recognized phosphorylated wild-type PLCgamma2 on Western blots but did not interact with unphosphorylated PLCgamma2 or with PLCgamma2 containing mutated tyrosine…

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PLCγ2 is phosphorylated at four tyrosines: Y753, Y759, Y1197, and Y1217.
“PLCγ2 would then be phosphorylated at four tyrosines (Y753, Y759, Y1197, and Y1217 (8, 9, 10, 11)).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [8]

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Activation of Phospholipase C 2 by Tyrosine Phosphorylation
Özdener, F., Dangelmaier, C., Ashby, B., & Kunapuli, S. P. (2002) · Cited by 8 · see citing works
Self-citation
Tyrosine Residues in Phospholipase Cγ2 Essential for the Enzyme Function in B-cell Signaling
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A New Tyrosine Phosphorylation Site in PLCγ1: The Role of Tyrosine 775 in Immune Receptor Signaling
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Authors: Özdener, F., Dangelmaier, C., Ashby, B., Kunapuli, S. P., & Daniel, J. L.
Affiliations: Temple University (US)
ORCID: Özdener, Fatih
Dangelmaier, Carol
Kunapuli, Satya P.
Venue: Molecular Pharmacology
Publisher: Elsevier BV
Published: 2002-09
Volume: 62
Issue: 3
Pages: 672-679
ISSN: 0026-895X (ISSN-L)
DOI: 10.1124/mol.62.3.672
OpenAlex: W1829376516
Cited by: 60
References: 37
Citations by year: 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 1
FWCI: 1.86
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Molecular Pharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-60683, R01HL060683)
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 › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: PLCγ2, tyrosine phosphorylation, tyrosine kinase activation, Lck, Fyn, Lyn kinase, platelets, phospho-specific antibodies, calcium-dependent enzyme activity
MeSH terms: Blood Platelets, Enzyme Activation, Humans, Isoenzymes, Type C Phospholipases, Phosphorylation, Proto-Oncogene Proteins, Recombinant Proteins, Tyrosine, Mutagenesis, Site-Directed, src Homology Domains, src-Family Kinases, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Proto-Oncogene Proteins c-fyn, Phospholipase C gamma, In Vitro Techniques

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Activation of Phospholipase Cγ2 by Tyrosine Phosphorylation

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