Cloning and Characterization of a Novel Class II Phosphoinositide 3-Kinase Containing C2 Domain

1998 ◽  
Vol 244 (2) ◽  
pp. 531-539 ◽  
Author(s):  
Hiroyuki Misawa ◽  
Motoaki Ohtsubo ◽  
Neal G. Copeland ◽  
Debra J. Gilbert ◽  
Nancy A. Jenkins ◽  
...  
Keyword(s):  
Class Ii ◽  
C2 Domain ◽  
Phosphoinositide 3 Kinase

Epidermal growth factor stimulates translocation of the class II phosphoinositide 3-kinase PI3K-C2β to the nucleus

2009 ◽  
Vol 422 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Hrvoje Banfic ◽  
Dora Visnjic ◽  
Nikica Mise ◽  
Sanjeevi Balakrishnan ◽  
Simona Deplano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Nuclear Localization ◽  
Mammalian Cells ◽  
Class Ii ◽  
Kinase Assay ◽  
C2 Domain ◽  
Protein Fusion ◽  
Epidermal Growth ◽  
Phosphoinositide 3 Kinase

Although the class II phosphoinositide 3-kinase enzymes PI3K-C2α and PI3K-C2β act acutely downstream of cell surface receptors they have also been localized to nuclei in mammalian cells. As with the class I PI3K enzymes, the relationship between the pools of enzyme present in cytoplasm and nuclei remains poorly understood. In this study we test the hypothesis that PI3K-C2β translocates to nuclei in response to growth factor stimulation. Fractionating homogenates of quiescent cells revealed that less than 5% of total PI3K-C2β resides in nuclei. Stimulation with epidermal growth factor sequentially increased levels of this enzyme, firstly in the cytosol and secondly in the nuclei. Using detergent-treated nuclei, we showed that PI3K-C2β co-localized with lamin A/C in the nuclear matrix. This was confirmed biochemically, and a phosphoinositide kinase assay showed a statistically significant increase in nuclear PI3K-C2β levels and lipid kinase activity following epidermal growth factor stimulation. C-terminal deletion and point mutations of PI3K-C2β demonstrated that epidermal growth factor-driven translocation to the nucleus is dependent on a sequence of basic amino acid residues (KxKxK) that form a nuclear localization motif within the C-terminal C2 domain. Furthermore, when this sequence was expressed as an EGFP (enhanced green fluorescent protein) fusion protein, it translocated fluorescence into nuclei with an efficiency dependent upon copy number. These data demonstrate that epidermal growth factor stimulates the appearance of PI3K-C2β in nuclei. Further, this effect is dependent on a nuclear localization signal present within the C-terminal C2 domain, indicating its bimodal function regulating phospholipid binding and shuttling PI3K-C2β into the nucleus.

scholarly journals Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin

1997 ◽  
Vol 326 (1) ◽  
pp. 139-147 ◽  
Author(s):  
Jan DOMIN ◽  
Françoise PAGES ◽  
Stefano VOLINIA ◽  
Susan E. RITTENHOUSE ◽  
Marketa J. ZVELEBIL ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Biochemical Analysis ◽  
Cellular Responses ◽  
C2 Domain ◽  
Substrate Specificities ◽  
Sequence Heterogeneity ◽  
Phosphoinositide 3 Kinase ◽  
Lipid Substrate ◽  
K Activity

The generation of phosphatidylinositide 3-phosphates has been observed in a variety of cellular responses. The enzymes that mediate synthesis are the phosphoinositide 3-kinases (PI3-Ks) that form a family of structurally diverse enzymes with distinct substrate specificities. In this paper, we describe the cloning of a novel human PI3-K, namely PI3-K-C2α, which contains a C-terminal C2 domain. This enzyme can be assigned to the class II PI3-Ks, which was defined by characterization of the Drosophila 68D enzyme and includes the recently described murine enzymes m-cpk and p170. Despite the overall similarity in the amino acid sequence of the murine and human enzymes, which suggests that they are encoded by closely related genes, these molecules show marked sequence heterogeneity at their N-termini. Biochemical analysis of recombinant PI3-K-C2α demonstrates a restricted lipid substrate specificity. As reported for other members of this class, the enzyme only phosphorylates PtdIns and PtdIns4P when the lipids are presented alone. However, when lipids were presented together with phosphatidylserine acting as a carrier, phosphorylation of PtdIns(4,5)P2 was also observed. The catalytic activity of PI3-K-C2α is refractory to concentrations of wortmannin and LY294002 which inhibit the PI3-K activity of other family members. The comparative insensitivity of PI3-K-C2α to these inhibitors suggests that their use should be re-evaluated in the study of PI3-Ks.

cDNA Cloning of a Third Human C2-Domain-Containing Class II Phosphoinositide 3-Kinase, PI3K-C2γ, and Chromosomal Assignment of This Gene (PIK3C2G) to 12p12

Genomics ◽  
1998 ◽  
Vol 54 (3) ◽  
pp. 569-574 ◽  
Author(s):  
Magdalena Rozycka ◽  
Yong-Jie Lu ◽  
Richard A. Brown ◽  
Mike R. Lau ◽  
Janet M. Shipley ◽  
...  
Keyword(s):  
Cdna Cloning ◽  
Class Ii ◽  
Chromosomal Assignment ◽  
C2 Domain ◽  
Phosphoinositide 3 Kinase

scholarly journals Purification and characterization of class II histocompatibility antigens from a homozygous human B cell line.

1987 ◽  
Vol 262 (33) ◽  
pp. 16087-16094
Author(s):  
J C Gorga ◽  
V Horejsí ◽  
D R Johnson ◽  
R Raghupathy ◽  
J L Strominger
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Class Ii ◽  
Purification And Characterization ◽  
Histocompatibility Antigens ◽  
Human B Cell

Characterization of class II fumarase from Schistosoma mansoni provides the molecular basis for selective inhibition

2021 ◽  
Vol 175 ◽  
pp. 406-421
Author(s):  
Iara Aimê Cardoso ◽  
Aline Kusumota Luiz de Souza ◽  
Adam Muslem George Burgess ◽  
Iain Wyllie Chalmers ◽  
Karl Francis Hoffmann ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Molecular Basis ◽  
Selective Inhibition ◽  
Class Ii

scholarly journals Characterization of Multiple C2 Domain and Transmembrane Region Proteins in Arabidopsis

2017 ◽  
Vol 176 (3) ◽  
pp. 2119-2132 ◽  
Author(s):  
Lu Liu ◽  
Chunying Li ◽  
Zhe Liang ◽  
Hao Yu
Keyword(s):  
C2 Domain ◽  
Transmembrane Region

Characterization of the Membrane Binding Mode of the C2 Domain of PKCε†

Biochemistry ◽  
2003 ◽  
Vol 42 (40) ◽  
pp. 11661-11668 ◽  
Author(s):  
Senena Corbalán-Garcia ◽  
Susana Sánchez-Carrillo ◽  
Josefa García-García ◽  
Juan C. Gómez-Fernández
Keyword(s):  
Membrane Binding ◽  
Binding Mode ◽  
C2 Domain

Characterization of bovine MHC class II DRB3 diversity in South American Holstein cattle populations

2015 ◽  
Vol 86 (6) ◽  
pp. 419-430 ◽  
Author(s):  
S.-N. Takeshima ◽  
G. Giovambattista ◽  
N. Okimoto ◽  
Y. Matsumoto ◽  
A. Rogberg-Muñoz ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Class Ii ◽  
Holstein Cattle ◽  
South American
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