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JNK- and Rac1-dependent induction of immediate early gene pip92 suppresses neuronal differentiation.
J Neurochem. 2007 Jan; 100(2):555-66.JN

Abstract

The immediate early gene pip92 is rapidly and transiently induced by serum, basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and phobol ester, as well as various toxic stimuli. Rho GTPases, such as RhoA, Rac1 and Cdc42, have been implicated in both cytoskeletal rearrangement and cell cycle control. Rac1 and Cdc42 induce neurite outgrowth in many types of neuronal cells. A downstream effector of both Rac1 and Cdc42, p21-activated kinase (Pak1), is highly enriched in neurons. In the present study, we examined the signal transduction pathways involved in pip92 induction, focusing on the involvement of Rho family guanosine 5'-triphosphate (GTP)ases. We also examined the functional role of pip92 expression during FGF-induced neuronal differentiation in embryonic hippocampal cells. Significant and robust activation of c-Jun N-terminal Kinase (JNK), Rac1 and extracellular signal-regulated kinase (ERK) appeared to be important for pip92 induction in response to bFGF. Transient transfection of kinase-inactive MEKK7 or chemical inhibitors of JNK significantly decreased the activation of Rac1 by FGF. However, blockade of Rac1 did not affect JNK activity. Moreover, a MEK-ERK blockade did not affect Rac1 activity. Activation of JNK and Rac1 induced Pak1 activity, which could then phosphorylate and activate transcription factor Elk1. Stimulation of Pak1-dependent Elk1 was required for the bFGF-induced activation of pip92. Suppression of endogenous pip92 expression by siRNA significantly enhanced bFGF-induced neurite outgrowth, while the ectopic expression of pip92 suppressed the neurite extension. Taken together, these data suggest that neurogenic growth factor-induced expression of pip92 is critical for the regulation of neuronal differentiation, occurring through the subsequent activation of Rac1, JNK, Pak1 and Elk1.

Authors+Show Affiliations

Department of Medical Science, Yonsei University College of Medicine, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17156131

Citation

Park, Jung Bum, et al. "JNK- and Rac1-dependent Induction of Immediate Early Gene Pip92 Suppresses Neuronal Differentiation." Journal of Neurochemistry, vol. 100, no. 2, 2007, pp. 555-66.
Park JB, Kim EJ, Yang EJ, et al. JNK- and Rac1-dependent induction of immediate early gene pip92 suppresses neuronal differentiation. J Neurochem. 2007;100(2):555-66.
Park, J. B., Kim, E. J., Yang, E. J., Seo, S. R., & Chung, K. C. (2007). JNK- and Rac1-dependent induction of immediate early gene pip92 suppresses neuronal differentiation. Journal of Neurochemistry, 100(2), 555-66.
Park JB, et al. JNK- and Rac1-dependent Induction of Immediate Early Gene Pip92 Suppresses Neuronal Differentiation. J Neurochem. 2007;100(2):555-66. PubMed PMID: 17156131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - JNK- and Rac1-dependent induction of immediate early gene pip92 suppresses neuronal differentiation. AU - Park,Jung Bum, AU - Kim,Eun Joo, AU - Yang,Eun Jin, AU - Seo,Su Ryeon, AU - Chung,Kwang Chul, Y1 - 2006/11/29/ PY - 2006/12/13/pubmed PY - 2007/3/7/medline PY - 2006/12/13/entrez SP - 555 EP - 66 JF - Journal of neurochemistry JO - J Neurochem VL - 100 IS - 2 N2 - The immediate early gene pip92 is rapidly and transiently induced by serum, basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and phobol ester, as well as various toxic stimuli. Rho GTPases, such as RhoA, Rac1 and Cdc42, have been implicated in both cytoskeletal rearrangement and cell cycle control. Rac1 and Cdc42 induce neurite outgrowth in many types of neuronal cells. A downstream effector of both Rac1 and Cdc42, p21-activated kinase (Pak1), is highly enriched in neurons. In the present study, we examined the signal transduction pathways involved in pip92 induction, focusing on the involvement of Rho family guanosine 5'-triphosphate (GTP)ases. We also examined the functional role of pip92 expression during FGF-induced neuronal differentiation in embryonic hippocampal cells. Significant and robust activation of c-Jun N-terminal Kinase (JNK), Rac1 and extracellular signal-regulated kinase (ERK) appeared to be important for pip92 induction in response to bFGF. Transient transfection of kinase-inactive MEKK7 or chemical inhibitors of JNK significantly decreased the activation of Rac1 by FGF. However, blockade of Rac1 did not affect JNK activity. Moreover, a MEK-ERK blockade did not affect Rac1 activity. Activation of JNK and Rac1 induced Pak1 activity, which could then phosphorylate and activate transcription factor Elk1. Stimulation of Pak1-dependent Elk1 was required for the bFGF-induced activation of pip92. Suppression of endogenous pip92 expression by siRNA significantly enhanced bFGF-induced neurite outgrowth, while the ectopic expression of pip92 suppressed the neurite extension. Taken together, these data suggest that neurogenic growth factor-induced expression of pip92 is critical for the regulation of neuronal differentiation, occurring through the subsequent activation of Rac1, JNK, Pak1 and Elk1. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/17156131/JNK__and_Rac1_dependent_induction_of_immediate_early_gene_pip92_suppresses_neuronal_differentiation_ L2 - https://doi.org/10.1111/j.1471-4159.2006.04263.x DB - PRIME DP - Unbound Medicine ER -