LIM kinase 1 activates cAMP-responsive element-binding protein during the neuronal differentiation of immortalized hippocampal progenitor cells.
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.
Yang
Eun Jin
EJ
Department of Biology, College of Sciences, Yonsei University, Seoul 120-749, Korea.
Yoon
Joo-Heon
JH
Min
Do Sik
DS
Chung
Kwang Chul
KC
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002461:Cell Line, Transformed; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D054461:Lim Kinases; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D011494:Protein Kinases; D054461:Lim Kinases; C515894:Limk1 protein, rat; D017346:Protein Serine-Threonine Kinases