Role of the p55-gamma subunit of PI3K in ALK-induced cell migration: RNAi-based selection of cell migration regulators.
Recently, unbiased functional genetic selection identified novel cell migration-regulating genes. This RNAi-based functional selection was performed using 63,996 pooled lentiviral shRNAs targeting 21,332 mouse genes. After five rounds of selection using cells with accelerated or impaired migration, shRNAs were retrieved and identified by half-hairpin barcode sequencing using cells with the selected phenotypes. This selection process led to the identification of 29 novel cell migration regulators. One of these candidates, anaplastic lymphoma kinase (ALK), was further investigated. Subsequent studies revealed that ALK promoted cell migration through the PI3K-AKT pathway via the p55γ regulatory subunit of PI3K, rather than more commonly used p85 subunit. Western blot and immunohistochemistry studies using mouse brain tissues revealed similar temporal expression patterns of ALK, phospho-p55γ, and phospho-AKT during different stages of development. These data support an important role for the p55γ subunit of PI3K in ALK-induced cell migration during brain development.
a Department of Agricultural Biology , National Institute of Agricultural Sciences, RDA , Wanju-gun , Republic of Korea.|b Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program , Kyungpook National University School of Medicine , Daegu , Republic of Korea.
Minchul
M
Seo
b Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program , Kyungpook National University School of Medicine , Daegu , Republic of Korea.
Jong-Heon
JH
Kim
b Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program , Kyungpook National University School of Medicine , Daegu , Republic of Korea.
Kyoungho
K
Suk
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D001921:Brain / Q000254:growth & development; D002465:Cell Movement / Q000235:genetics*; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018390:Gene Targeting; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D058543:Class Ia Phosphatidylinositol 3-Kinase; C523442:PIK3R3 protein, human; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt
ALK; PI3K; RNAi; brain development; cell migration