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Bruton's tyrosine kinase phosphorylates cAMP-responsive element-binding protein at serine 133 during neuronal differentiation in immortalized hippocampal progenitor cells

 Eun Jin Yang  ;  Joo-Heon Yoon  ;  Kwang Chul Chung 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.279(3) : 1827-1837, 2004 
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Agammaglobulinaemia Tyrosine Kinase ; Animals ; Cell Differentiation ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Enzyme Activation ; Epidermal Growth Factor/pharmacology ; Fibroblast Growth Factor 2/pharmacology ; Hippocampus/cytology ; Hippocampus/metabolism* ; Mice ; Mitogen-Activated Protein Kinases/physiology ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism* ; RNA, Small Interfering/physiology ; Response Elements ; Serine/metabolism* ; Signal Transduction ; Stem Cells/metabolism*
Bruton's tyrosine kinase (BTK) is a member of the Tec family of kinases, which is a subgroup of the nonreceptor cytoplasmic protein tyrosine kinases. BTK has been shown to be important in the proliferation, differentiation, and signal transduction of B cells. Mutations in BTK result in B cell immune deficiency disorders, such as X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Although BTK plays multiple roles in the life of a B cell, its functional role in neuronal cells has not been elucidated. In the present study, we demonstrate that BTK activates transcription factor, cAMP response element (CRE)-binding protein (CREB), and subsequent CRE-mediated gene transcription during basic fibroblast growth factor (bFGF)-induced neuronal differentiation in immortalized hippocampal progenitor cells (H19-7). The kinase activity of BTK is also induced by bFGF, and BTK directly phosphorylates CREB at Ser-133 residue, indicating that BTK has a dual protein kinase activity. In addition, blockading BTK activation significantly inhibits CREB phosphorylation as well as the neurite outgrowth induced by bFGF in H19-7 cells. These results suggest that the activation of BTK and the subsequent phosphorylation of CREB at Ser-133 are important in the neuronal differentiation of hippocampal progenitor cells.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
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