Suppression of a phosphatidylinositol 3-kinase signal by a specific spliced variant of Drosophila PTEN.
Drosophila PTEN (dPTEN) plays indispensable roles in the development of Drosophila melanogaster by controlling cell size and number. Although three potential spliced forms of dPTEN have been isolated, functional distinction among these forms remains elusive. In this study, we demonstrate that all spliced forms of dPTEN dephosphorylate phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)); however, PI(3,4,5)P(3)-dependent activation of Drosophila Akt is suppressed specifically by one of three spliced forms, dPTEN3. Further, dPTEN3 dramatically changes its expression during the Drosophila development, while the other forms are expressed throughout the development. Our results suggest that dPTEN3 is the predominant spliced form that participates in PI(3,4,5)P(3)-mediated signaling pathways.
Maehama
Tomohiko
T
Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Tokyo 113-8613, Japan. tmaehama@rinshoken.or.jp
Kosaka
Natsuki
N
Okahara
Fumiaki
F
Takeuchi
Ken-ichi
K
Umeda
Masato
M
Dixon
Jack E
JE
Kanaho
Yasunori
Y
D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D004331:Drosophila melanogaster; D005982:Glutathione Transferase / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D018076:DNA, Complementary; D029721:Drosophila Proteins; D005982:Glutathione Transferase; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases; D012333:RNA, Messenger; D011994:Recombinant Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; C487101:PTEN protein, Drosophila