Table of Contents - *609763
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Genome
DNA
Protein
Gene Info
Variation
Animal Models
Cellular Pathways
| *609763 | ||||||||||||
| PHOSPHATIDYLINOSITOL 4-KINASE, TYPE 2, ALPHA; PI4K2A | ||||||||||||
| Alternative titles; symbols | ||||||||||||
| PHOSPHATIDYLINOSITOL 4-KINASE, TYPE II PI4KII PI4KII-ALPHA | ||||||||||||
| HGNC Approved Gene Symbol: PI4K2A | ||||||||||||
| Cytogenetic location: 10q24.2 Genomic coordinates (GRCh37): 10:99,400,442 - 99,436,186 (from NCBI) | ||||||||||||
| TEXT | ||||||||||||
| Description | ||||||||||||
| Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in many biologic processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates PtdIns at the D-4 position, an essential step in the biosynthesis of PtdInsPs (Barylko et al., 2001). | ||||||||||||
| Cloning | ||||||||||||
| Minogue et al. (2001) partially purified PI4KII from plasma membrane rafts isolated from human A431 epidermoid carcinoma cells. By peptide sequencing, database analysis, and RT-PCR of A431 total RNA, they obtained a full-length PI4KII cDNA. The deduced 479-amino acid protein has a calculated molecular mass of about 54 kD. PI4KII has a kinase domain and a leucine zipper, but no transmembrane sequence or acylation motif. Northern blot analysis detected a 6.6-kb transcript in all tissues examined. Expression was highest in kidney, brain, heart, skeletal muscle, and placenta, and was lowest in colon, thymus, and small intestine. Purified PI4KII had an apparent molecular mass of 52 kD by SDS-PAGE. Barylko et al. (2001) identified a cysteine-rich segment (CCPCC), a potential palmitoylation site, in rat and human PI4KII. By immunofluorescence localization, Wang et al. (2003) found that PI4KII localized to the Golgi in transfected COS-7 cells. | ||||||||||||
| Gene Function | ||||||||||||
| Minogue et al. (2001) assayed recombinant PI4KII expressed in bacteria and found that it phosphorylated PtdIns, but not PtdIns3P, PtdIns4P, or PtdIns5P. Like PI4KII purified from tissues, recombinant PI4KII was activated by detergent and inhibited by adenosine. Wang et al. (2003) found that overexpression of PI4KII in COS-7 cells increased synthesis of PtdIns4P. Some cells overexpressing PI4KII had scattered or no perinuclear Golgi. Knockdown of PI4KII by RNA interference (RNAi) did not disrupt the Golgi, and some cells showed expanded Golgi. RNAi reduced the Golgi level of PtdIns4P and blocked the association between AP1 (see 607291) and the trans-Golgi network (TGN). PI4KII RNAi had little effect on intra-Golgi trafficking, but it inhibited TGN-to-plasma membrane export by 35%. Wang et al. (2003) proposed that PI4KII generates PtdIns4P-rich domains within the Golgi that specify docking of the AP1 coat machinery. By screening a human kinase small interfering RNA library, Pan et al. (2008) identified PI4KII-alpha and phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI; 603275) as required for Wnt3a (606359)-induced LRP6 (603507) phosphorylation at ser1490 in mammalian cells and confirmed that these kinases are important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates through 'frizzled' (see 603408) and 'dishevelled' (see 601365), the latter of which directly interacted with and activated PIP5KI. In turn, phosphatidylinositol 4,5-bisphosphates regulated phosphorylation of LRP6 at thr1479 and ser1490. Pan et al. (2008) concluded that their study revealed a signaling mechanism for Wnt to regulate LRP6 phosphorylation. | ||||||||||||
| Mapping | ||||||||||||
| The International Radiation Hybrid Mapping Consortium mapped the PI4K2A gene to chromosome 10 (H66059). | ||||||||||||
| REFERENCES | ||||||||||||
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