Cell type specificity of PI3K signaling in Pdk1- and Pten-deficient brains.
Loss of PTEN causes unregulated activation of downstream components of phosphatidylinositol 3-kinase (PI3K) signaling, including PDK1, and disrupts normal nervous system development and homeostasis. We tested the contribution of Pdk1 to the abnormalities induced by Pten deletion in the brain. Conditional deletion of Pdk1 caused microcephaly. Combined deletion of Pdk1 and Pten rescued hypertrophy, but not migration defects of Pten-deficient neurons. Pdk1 inactivation induced strikingly different effects on the regulation of phosphorylated Akt in glia versus neurons. Our results show Pdk1-dependent and Pdk1-independent abnormalities in Pten-deficient brains, and demonstrate cell type specific differences in feedback regulation of the ubiquitous PI3K pathway.
Chalhoub
Nader
N
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Zhu
Guo
G
Zhu
Xiaoyan
X
Baker
Suzanne J
SJ
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases; D054868:Jacobsen Distal 11q Deletion Syndrome; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D064413:3-Phosphoinositide-Dependent Protein Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C421683:Pik3cd protein, mouse; C514862:Akt1 protein, mouse; C578564:Pdpk1 protein, mouse