Leucine-rich glioma inactivated 3 induces neurite outgrowth through Akt and focal adhesion kinase.
Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein that belongs to LGI/epitempin family. LGI3 is highly expressed in brain in a transcriptionally and developmentally regulated manner. Here we found that LGI3 induced neurite outgrowth in Neuro-2a cells and dorsal root ganglia explants. LGI3 treatment or overexpression increased neurite outgrowth and knockdown of LGI3 by siRNA had opposite effect. LGI3 treatment increased phosphorylation of Akt and a 125-kDa protein. Immunoprecipitation identified the 125-kDa protein as focal adhesion kinase (FAK). LGI3 overexpression increased phospho-Akt, phospho-FAK and FAK protein. Inhibition of Akt activation by PI3 kinase inhibitor attenuated LGI3-induced FAK phosphorylation and neurite outgrowth. Taken together, we propose that LGI3 is a neuritogenic factor whose signaling pathway involves Akt-mediated FAK activation.
Park
Woo-Jae
WJ
Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul, 156-756, Republic of Korea.
Lim
Yun Young
YY
Kwon
Nyoun Soo
NS
Baek
Kwang Jin
KJ
Kim
Dong-Seok
DS
Yun
Hye-Young
HY
D000818:Animals; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D005727:Ganglia, Spinal / Q000254:growth & development; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*
D002867:Chromones; C511168:LGI3 protein, mouse; D009025:Morpholines; D009419:Nerve Tissue Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt