| First Author | Bi L | Year | 1999 |
| Journal | J Biol Chem | Volume | 274 |
| Issue | 16 | Pages | 10963-8 |
| PubMed ID | 10196176 | Mgi Jnum | J:54237 |
| Mgi Id | MGI:1334821 | Doi | 10.1074/jbc.274.16.10963 |
| Citation | Bi L, et al. (1999) Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. J Biol Chem 274(16):10963-8 |
| abstractText | Phosphatidylinositol 3,4,5-trisphosphate is a phospholipid signaling molecule involved in many cellular functions including growth factor receptor signaling, cytoskeletal organization, chemotaxis, apoptosis, and protein trafficking. Phosphorylation at the 3 position of the inositol ring is catalyzed by many different 3-kinases (classified as types I-A, I-B, II, and III), but the physiological roles played by each of the different 3- kinase isozymes during embryonic development and in homeostasis in animals is incompletely understood, Mammalian type I-A kinase isozymes are heterodimers that are active at 37 degrees C when the catalytic 110-kDa subunit interacts through an amino-terminal binding domain with a regulatory 85- or 55-kDa subunit, Using gene targeting in embryonic stem cells, we deleted this binding domain in the gene encoding the alpha isoform of the 110- kDa catalytic subunit (Pik3ca) of the alpha isozyme of the type I-A kinases, leading to loss of expression of the p110 catalytic subunit. We show that Pik3ca(del/del) embryos are developmentally delayed at embryonic day (E) 9.5 and die between E9.5 and E10.5. E9.5 Pik3ca(del/del) embryos have a profound proliferative defect but no increase in apoptosis, A proliferative defect is supported by the observation that fibroblasts from Pik3ca(del/del) embryos fail to replicate in Dulbecco's modified Eagle's medium and fetal calf serum, even with supplemental growth factors. |
