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Fransson, S., Uv, A., Eriksson, H., Andersson, M.K., Wettergren, Y., Bergo, M., Ejeskär, K. (2012). p37δ is a new isoform of PI3K p110δ that increases cell proliferation and is overexpressed in tumors.  Oncogene 31(27): 3277--3286.
FlyBase ID
FBrf0219466
Publication Type
Research paper
Abstract

The phosphatidylinositol 3-kinases (PI3Ks) regulate cell growth, proliferation and survival, and are frequently affected in human cancer. PI3K is composed of a catalytic subunit, p110, and a regulatory subunit, p85. The PI3K catalytic subunit p110δ is encoded by PIK3CD and contains p85- and RAS-binding domains, and a kinase domain. Here we present an alternatively spliced PIK3CD transcript encoding a previously unknown protein, p37δ, and demonstrate that this protein is expressed in human ovarian and colorectal tumors. p37δ retains the p85-binding domain and a fraction of the RAS-binding domain, lacks the catalytic domain, and has a unique carboxyl-terminal region. In contrast to p110δ, which stabilizes p85, p37δ promoted p85 sequestering. Despite the truncated RAS-binding domain, p37δ bound to RAS and we found a strong positive correlation between the protein levels of p37δ and RAS. Overexpressing p37δ, but not p110δ, increased the proliferation and invasive properties of HEK-293 cells and mouse embryonic fibroblasts. Cells overexpressing p37δ showed a quicker phosphorylation response of AKT and ERK1/2 following serum stimulation. Ubiquitous expression of human p37δ in the fruit fly increased body size, DNA content and phosphorylated ERK1/2 levels. Thus, p37δ appears to be a new tumor-specific isoform of p110δ with growth-promoting properties.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Oncogene
    Title
    Oncogene
    Publication Year
    1987-
    ISBN/ISSN
    0950-9232
    Data From Reference
    Alleles (2)
    Genes (3)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (2)