PLCG1

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PLCG1
Protein PLCG1 PDB 1hsq.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PLCG1, NCKAP3, PLC-II, PLC1, PLC148, PLCgamma1, phospholipase C gamma 1
External IDs MGI: 97615 HomoloGene: 1997 GeneCards: PLCG1
Gene location (Human)
Chromosome 20 (human)
Chr. Chromosome 20 (human)[1]
Chromosome 20 (human)
Genomic location for PLCG1
Genomic location for PLCG1
Band 20q12 Start 41,136,960 bp[1]
End 41,196,801 bp[1]
RNA expression pattern
PBB GE PLCG1 202789 at fs.png

PBB GE PLCG1 216551 x at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002660
NM_182811

NM_021280

RefSeq (protein)

NP_002651
NP_877963

NP_067255

Location (UCSC) Chr 20: 41.14 – 41.2 Mb Chr 20: 160.73 – 160.78 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Phospholipase C, gamma 1, also known as PLCG1, is a protein that in humans is encoded by the PLCG1 gene.[5][6]

Function[edit]

The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to translocate to the Golgi apparatus, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. The receptor protein tyrosine phosphatase PTPmu (PTPRM) is capable of dephosphorylating PLCG1.[7] Two transcript variants encoding different isoforms have been found for this gene.[8]

Common to all PLC isozymes, PLCG1 consists of an N-terminal PH domain, which translocates PLC to the plasma membrane and binds PIP3;[9] four EF hands; an X and Y catalytic region comprising the TIM barrel; and a C-terminal C2 domain.[10] Specific to the PLCG isozymes is a large separation between the X and Y domains consisting of a split PH domain, tandem SH2 domains, and an SH3 domain.[10] The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the catalytic function of PLCg; and the SH3 domain binds to proline-rich sequences on the target protein.[10]

PLCG1 can be activated by receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases. For example, when activated, fibroblast growth factor receptor 1 and epidermal growth factor receptor are RTKs that have phosphorylated tyrosines, which provide docking sites for PLCG1 SH2 domains.[10] The activated RTKs phosphoylate PLCG1 at tyrosines located at position 472, 771, 775, 783, and 1254.[11] Non-receptor tyrosine kinases interact with PLCG1 in large complexes at the plasma membrane. For example, in T cells, Lck and Fyn (Src family kinases) phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the T-cell antigen receptor (TCR).[10] The phosphorylated ITAMs recruit ZAP-70, which phosphorylates tyrosines in LAT and SLP-76. PLCg1 binds to LAT through its n-terminal SH2 domain and to SLP-76 via its SH3 domain.[10]

Has been shown to interact with CISH which negatively regulates it by targeting it for degradation.[12] The deletion of Cish in effector T cells has been shown to augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. There are no changes in activity or phosphorylation of Cish's purported target, STAT5 in either the presence or absence of Cish.

Clinical significance[edit]

Researchers studying PLCg1 and its role in breast cancer metastasis discovered this gene can promote cancer metastasis and subsequently blocking it stopped cancer from spreading. Research is ongoing but this gene could lead to the development of new anti-cancer drugs.[13][14]

Interactions[edit]

PLCG1 has been shown to interact with:

See also[edit]

References[edit]

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  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000016933 - Ensembl, May 2017
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