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

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23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1827-1837
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number3
DOIs
Publication statusPublished - 2004 Jan 16

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Serine
Carrier Proteins
Stem Cells
Fibroblast Growth Factor 2
Phosphorylation
B-Lymphocytes
Cells
Phosphotransferases
Chemical activation
Agammaglobulinaemia tyrosine kinase
Cyclic AMP Response Element-Binding Protein
Signal transduction
Immune System Diseases
Response Elements
Transcription
Protein-Tyrosine Kinases
Protein Kinases
Signal Transduction
Transcription Factors
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "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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