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PHOSPHATIDYLINOSITOL 4-KINASE, TYPE 2, BETA; PI4K2B

PHOSPHATIDYLINOSITOL 4-KINASE, TYPE 2, BETA; PI4K2B

Alternative titles; symbolsPHOSPHATIDYLINOSITOL 4-KINASE, TYPE II, BETAPI4KII-BETAHGNC Approved Gene Symbol: PI4K2BCytogenetic location: 4p15.2 Genomic coord...

Alternative titles; symbols

  • PHOSPHATIDYLINOSITOL 4-KINASE, TYPE II, BETA
  • PI4KII-BETA

HGNC Approved Gene Symbol: PI4K2B

Cytogenetic location: 4p15.2 Genomic coordinates (GRCh38): 4:25,234,032-25,279,203 (from NCBI)

▼ Description
Phosphatidylinositol 4-kinases (PI4Ks) phosphorylate phosphatidylinositol to generate phosphatidylinositol 4-phosphate (PIP), an immediate precursor of several important signaling and scaffolding molecules. PIP itself may also have direct functional and structural roles. PI4K2B is a primarily cytosolic PI4K that is recruited to membranes, where it stimulates phosphatidylinositol 4,5-bisphosphate synthesis (Wei et al., 2002).

▼ Cloning and Expression
By searching databases for homologs of PI4K2A (609763), Balla et al. (2002) identified PI4K2B. The deduced 490-amino acid PI4K2B protein has a calculated molecular mass of 54 kD and differs from PI42KA primarily in the N terminus. Northern blot analysis showed ubiquitous expression of a 3.8-kb primary PI4K2B transcript. Relative to PI4K2A, expression of PI4K2B was higher in liver, but lower in brain and peripheral blood leukocytes. Confocal microscopy revealed expression of PI4K2B in intracellular membranes, particularly in early endosomes, as indicated by colocalization with EEA1 (605070). PI4K2B showed little or no colocalization with Golgi bodies, and its N-terminal region was required for membrane localization.

Using PCR, Wei et al. (2002) cloned PI4K2B. Immunofluorescence microscopy and subcellular fractionation showed that PI4K2B was primarily cytosolic and that it associated peripherally with plasma membranes, endoplasmic reticulum, and Golgi in HeLa and COS-7 cells. In contrast, PI4K2A was predominantly associated with Golgi.

▼ Gene Function
Balla et al. (2002) found that expression of PI4K2B in COS-7 cells increased PI4K activity, which was associated with microsomal membrane fractions. However, PI4K2B activity was significantly lower than that of PI4K2A. Both enzymes used phosphatidylinositol as their primary substrate and had no activity on phosphatidylinositol monophosphates.

Wei et al. (2002) found that expression of constitutively active RAC1 (602048) recruited PI4K2B to the plasma membrane and increased its enzymatic activity. In contrast, dominant-negative RAC1 blocked PI4K2B membrane association and inhibited PI4K2B activity. Microsome-bound PI4K2B was 16 times more active than cytosolic PI4K2B. Membrane-bound PI4K2B was as active as membrane-bound PI4K2A and had the same kinetic properties. Wei et al. (2002) concluded that PI4K2A and PI4K2B have overlapping, but not identical, functions.

Griffioen et al. (2008) identified PI4K2B as an HLA-DQB1*0603-restricted minor histocompatibility antigen in a patient successfully treated with donor lymphocyte infusions for relapsed chronic myeloid leukemia after allogeneic stem cell transplantation. T cells specific for the PI4K2B antigen lysed normal and malignant hematopoietic cells, suggesting an involvement in antitumor immunity.

▼ Mapping
Gross (2017) mapped the PI4K2B gene to chromosome 4p15.2 based on an alignment of the PI4K2B sequence (GenBank AF411320) with the genomic sequence (GRCh38).

Tags: 4p15.2