全周 (9AM - 6PM)

我们和你在一起

Extra info thumb
PHOSPHOLIPASE C, BETA-2; PLCB2

PHOSPHOLIPASE C, BETA-2; PLCB2

HGNC Approved Gene Symbol: PLCB2Cytogenetic location: 15q15.1 Genomic coordinates (GRCh38): 15:40,285,495-40,307,944 (from NCBI)▼ DescriptionPhosphoinositide...

HGNC Approved Gene Symbol: PLCB2

Cytogenetic location: 15q15.1 Genomic coordinates (GRCh38): 15:40,285,495-40,307,944 (from NCBI)

▼ Description
Phosphoinositide-specific phospholipase C (PLC) plays a major role in transmembrane signaling by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and thereby generating the second messenger molecules inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. Several distinct PLC enzymes have been identified in a variety of mammalian tissues (summary by Park et al., 1992). PLCB2 participates in the T2R (see 604791) signal transduction pathway (summary by Shah et al., 2009).

▼ Cloning and Expression
Park et al. (1992) isolated cDNAs encoding a previously uncharacterized PLC by screening a human cDNA library derived from the promyelocytic cell line HL-60 with a bovine PLC-beta-1 (PLCB1) cDNA. The 1,181-amino acid protein predicted from the human cDNAs shares 48% amino acid identity with rat Plcb1 and is similar in overall structure to Plcb1; thus, it was named PLC-beta-2 (PLCB2). PLCB2 and Plcb1 show the least sequence similarity in their C-terminal 450 amino acids. PLCB2 contains the X and Y regions conserved among PLCs, and 1 PEST sequence, a motif suggesting sensitivity of PLCB2 to proteases. Recombinant PLCB2 expressed in mammalian cells migrated as a 140-kD protein in SDS-polyacrylamide gels. Characterization of recombinant PLCB2 revealed that the catalytic activity of PLCB2 is dependent on calcium and that PLCB2 prefers phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol as a substrate. Reconstitution experiments showed that alpha-q (600998), which is the alpha subunit of the pertussis toxin-insensitive G protein, activates Plcb1 but not PLCB2, suggesting that receptor-dependent stimulation of these 2 PLCBs may require different G protein alpha subunits.

▼ Gene Function
Santagata et al. (2001) demonstrated that tubby (601197) functions in signal transduction from heterotrimeric G protein-coupled receptors. Receptor-mediated activation of G-alpha-q releases tubby from the plasma membrane through the action of phospholipase C-beta, triggering translocation of tubby to the cell nucleus. The localization of tubby-like protein-3 (TULP3; 604730) is similarly regulated. Santagata et al. (2001) concluded that tubby proteins function as membrane-bound transcription regulators that translocate to the nucleus in response to phosphoinositide hydrolysis, providing a direct link between G protein signaling and the regulation of gene expression.

Rao et al. (1989), Yang et al. (1996), Lee et al. (1996), and Mao et al. (2002) described a unique platelet function defect characterized by a deficiency in platelet PLCB2 isozyme. The proposita and her son had impaired platelet aggregation, serotonin secretion, mobilization of cytoplasmic ionized calcium, and PLC activation in response to several G protein-coupled receptor-mediated agonists, including adenosine diphosphate (ADP), thrombin (176930), platelet-activating factor (173393), and thromboxane A2 (188070). Platelet levels of PLCB2 were decreased to approximately one-third with normal levels of other PLC isozymes. In further studies, Mao et al. (2002) found that PLCB2 mRNA and protein levels were decreased in platelets but normal in the neutrophils from the patient, which suggested a lineage-specific defect in PLCB2 gene expression. Mao et al. (2002) found no mutation in the coding sequence (cDNA) of the PLCB2 gene.

Shah et al. (2009) found that alpha-gustducin (139395) and PLCB2 are expressed in airway epithelia. Alpha-gustducin resides in the cilia, and PLCB2 appears to sit below the cilia in the apical portion of the cell. They also found that motile cilia emerging from human airway epithelial cells express sensory bitter taste receptors; see T2R4 (604869). Shah et al. (2009) concluded that airway epithelia contain a cell-autonomous system in which motile cilia both sense noxious substances entering airways and initiate a defensive mechanism to eliminate the offending compound. Hence, like primary cilia, classical motile cilia also contain sensors to detect the external environment.

Sun et al. (2013) showed that WDR26 (617424) bound PLCB2 and enhanced PLCB2 membrane translocation and activation by G-beta-gamma (see 139380) in human leukocytes.

▼ Mapping
By Southern blot analysis of a human/rodent somatic cell hybrid panel, Park et al. (1998) mapped the PLCB2 gene to chromosome 15. They localized the PLCB2 gene to 15q15 using FISH.

▼ Animal Model
Li et al. (2000) described the phenotype of mice lacking Plcb2 and Plcb3 (600230). The mice developed spontaneous multifocal skin ulcers usually starting at the age of 6 months or older. The lesions were localized mainly behind ears or on the neck, but sometimes also appeared on the face. The phenotype was similar to that of mice lacking Plcb3 alone.

Zhang et al. (2003) demonstrated that knockout of Trpm5 (604600), a taste TRP ion channel, or Plcb2, a phospholipase C selectively expressed in taste tissue, in mice abolished sweet, amino acid, and bitter taste reception, but did not affect sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction appeared to converge on common signaling molecules. Mice engineered to rescue PLCB2 function exclusively in bitter receptor-expressing cells responded normally to bitter tastants, but did not taste sweet or amino acid stimuli. The authors concluded that bitter is encoded independently of sweet and amino acids and that taste receptor cells are not broadly tuned across these modalities.

Tags: 15q15.1