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Cdo promotes neuronal differentiation via activation of the p38 mitogen‐activated protein kinase pathway
Author(s) -
Oh Ji-Eun,
Bae Gyu-Un,
Yang Youn-Joo,
Yi Min-Jeong,
Lee Hye-Jin,
Kim Bok-Geon,
Krauss Robert S.,
Kang Jong-Sun
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-119255
Subject(s) - microbiology and biotechnology , neurogenesis , protein kinase a , cdc42 , cellular differentiation , transcription factor , mapk/erk pathway , neural stem cell , cell fate determination , p38 mitogen activated protein kinases , p19 cell , kinase , scaffold protein , retinoic acid , signal transduction , biology , chemistry , stem cell , cell culture , biochemistry , adult stem cell , genetics , gene
Neural basic helix‐loop‐helix transcription factors (bHLHs) control many aspects of neurogenesis, such as proliferation, fate determination, and differentiation. We have previously shown that the promyogenic cell surface receptor Cdo modulates the Cdc42 and p38 mitogen‐activated protein kinase (MAPK) pathways via a direct association with two scaffold‐type proteins, JLP and Bnip‐2, to regulate activities of myogenic bHLH factors and myogenic differentiation. We report here that Cdo uses similar regulatory mechanisms to promote neuronal differentiation. Expression of JLP, a scaffold protein for p38MAPK, and Bnip‐2, a regulator of Cdc42, is increased during differentiation of C17.2 neural precursor cells and P19 embryonal carcinoma cells. These molecules regulate Cdc42 and p38MAPK activities, which increase in a Cdo‐dependent manner during neuronal differentiation of C17.2 cells and retinoic acid‐treated P19 cells. Furthermore, enhancement or reduction of Cdc42 and p38MAPK activities enhances or reduces, respectively, neuronal differentiation of these cell lines. Cdc42 and p38MAPK activities also promote heterodimerization of neurogenin1 and E47, suggesting that one way they promote neurogenesis is via regulation of neural bHLH factor activities. These results imply that a conserved intracellular signaling mechanism initiated by Cdo regulates the activities of tissue‐specific bHLH factors and therefore functions as a key regulator of differentiation of several different cell lineages.—Oh, J.‐E., Bae, G.‐U., Yang, Y.‐J., Yi, M.‐J., Lee, H.‐J., Kim, B.‐G., Krauss, R. S., Kang, J.‐S. Cdo promotes neuronal differentiation via activation of the p38 mitogen‐activated protein kinase pathway. FASEBJ. 23, 2088–2099 (2009)