LIM Kinase 1 Activates cAMP-responsive Element-binding Protein during the Neuronal Differentiation of Immortalized Hippocampal Progenitor Cells

Eun Jin Yang, Joo Heon Yoon, Do Sik Min, Kwang Chul Chung

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

LIM kinase 1 (LIMK1), a novel member of a subclass of the protein-serine/threonine kinases, is known to play a role in the development and maintenance of neuronal circuits that mediate cognitive function. Genetic studies have implicated a mutation of LIMK1 as a causative factor in the impairment of visuospatial cognition in a neurodevelopmental disorder, Williams syndrome. A transcriptional factor, cAMP-responsive element-binding protein (CREB), is thought to be involved in the formation of many types of synaptic plasticity involving learning and memory. In the present study we show that the LIMK1 activity is markedly induced during the differentiation of immortalized hippocampal progenitor (H19-7) cells. We found that the addition of neurogenic growth factor to H19-7 cells induces specific binding between LIMK1 and active CREB, that LIMK1 directly phosphorylates CREB, and that this leads to the stimulation of subsequent cAMP-responsive element-mediated gene transcription during H19-7 cell neuronal differentiation. In addition, we also found that LIMK1 activation occurs through Rac/Cdc42- and p21-activated kinase-mediated signaling pathways. Moreover, when the plasmid encoding kinase-inactive LIMK1 was transfected to block the activation of endogenous LIMK1, the neuronal differentiation of H19-7 cells was significantly suppressed. These findings suggest that LIMK1 activation and subsequent CREB phosphorylation are important in the neuronal differentiation of central nervous system hippocampal progenitor cells.

Original languageEnglish
Pages (from-to)8903-8910
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number10
DOIs
Publication statusPublished - 2004 Mar 5

Fingerprint

Lim Kinases
Carrier Proteins
Stem Cells
Chemical activation
Cognition
p21-Activated Kinases
Williams Syndrome
Phosphorylation
Neuronal Plasticity
Protein-Serine-Threonine Kinases
Neurology
Transcription
Protein Kinases
Plasticity
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Plasmids
Phosphotransferases
Central Nervous System
Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "LIM Kinase 1 Activates cAMP-responsive Element-binding Protein during the Neuronal Differentiation of Immortalized Hippocampal Progenitor Cells",
abstract = "LIM kinase 1 (LIMK1), a novel member of a subclass of the protein-serine/threonine kinases, is known to play a role in the development and maintenance of neuronal circuits that mediate cognitive function. Genetic studies have implicated a mutation of LIMK1 as a causative factor in the impairment of visuospatial cognition in a neurodevelopmental disorder, Williams syndrome. A transcriptional factor, cAMP-responsive element-binding protein (CREB), is thought to be involved in the formation of many types of synaptic plasticity involving learning and memory. In the present study we show that the LIMK1 activity is markedly induced during the differentiation of immortalized hippocampal progenitor (H19-7) cells. We found that the addition of neurogenic growth factor to H19-7 cells induces specific binding between LIMK1 and active CREB, that LIMK1 directly phosphorylates CREB, and that this leads to the stimulation of subsequent cAMP-responsive element-mediated gene transcription during H19-7 cell neuronal differentiation. In addition, we also found that LIMK1 activation occurs through Rac/Cdc42- and p21-activated kinase-mediated signaling pathways. Moreover, when the plasmid encoding kinase-inactive LIMK1 was transfected to block the activation of endogenous LIMK1, the neuronal differentiation of H19-7 cells was significantly suppressed. These findings suggest that LIMK1 activation and subsequent CREB phosphorylation are important in the neuronal differentiation of central nervous system hippocampal progenitor cells.",
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LIM Kinase 1 Activates cAMP-responsive Element-binding Protein during the Neuronal Differentiation of Immortalized Hippocampal Progenitor Cells. / Yang, Eun Jin; Yoon, Joo Heon; Min, Do Sik; Chung, Kwang Chul.

In: Journal of Biological Chemistry, Vol. 279, No. 10, 05.03.2004, p. 8903-8910.

Research output: Contribution to journalArticle

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