Pike. A nuclear gtpase that enhances PI3kinase activity and is regulated by protein 4.1N.
While cytoplasmic PI3Kinase (PI3K) is well characterized, regulation of nuclear PI3K has been obscure. A novel protein, PIKE (PI3Kinase Enhancer), interacts with nuclear PI3K to stimulate its lipid kinase activity. PIKE encodes a 753 amino acid nuclear GTPase. Dominant-negative PIKE prevents the NGF enhancement of PI3K and upregulation of cyclin D1. NGF treatment also leads to PIKE interactions with 4.1N, which has translocated to the nucleus, fitting with the initial identification of PIKE based on its binding 4.1N in a yeast two-hybrid screen. Overexpression of 4.1N abolishes PIKE effects on PI3K. Activation of nuclear PI3K by PIKE is inhibited by the NGF-stimulated 4.1N translocation to the nucleus. Thus, PIKE physiologically modulates the activation by NGF of nuclear PI3K.
Ye
K
K
Johns Hopkins University School of Medicine, Department of Neuroscience, North Wolfe Street 21205, Baltimore, MD, USA.
Hurt
K J
KJ
Wu
F Y
FY
Fang
M
M
Luo
H R
HR
Hong
J J
JJ
Blackshaw
S
S
Ferris
C D
CD
Snyder
S H
SH
D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D020932:Nerve Growth Factor / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D014162:Transfection; D020798:Two-Hybrid System Techniques; D018631:ras Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; C120557:erythrocyte membrane protein band 4.1-like 1; D019938:Cyclin D1; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C485997:AGAP2 protein, human; C418731:Agap2 protein, rat; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins