Bruton's tyrosine kinase phosphorylates cAMP-responsive element-binding protein at serine 133 during neuronal differentiation in immortalized hippocampal progenitor cells.
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.
Department of Biology, Yonsei University College of Sciences, Shinchon-dong 134, Seodaemun-gu, Seoul 120-749, Korea.
Eun Jin
EJ
Yang
Joo-Heon
JH
Yoon
Kwang Chul
KC
Chung
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000502:physiology; D020218:Response Elements; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D034741:RNA, Small Interfering; D016222:Fibroblast Growth Factor 2; D012694:Serine; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; D020928:Mitogen-Activated Protein Kinases