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Anti‐Thy‐1 antibody‐induced neurite outgrowth in cultured dorsal root ganglionic neurons is mediated by the c‐Src‐MEK signaling pathway
Author(s) -
Yang ShihHung,
Chen YiJen,
Tung PoYuan,
Lai WeiLing,
Chen Ying,
Jeng ChungJiuan,
Wang SeuMei
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21387
Subject(s) - neurite , creb , microbiology and biotechnology , protein kinase a , proto oncogene tyrosine protein kinase src , dorsal root ganglion , chemistry , kinase , signal transduction , biology , biochemistry , in vitro , transcription factor , anatomy , dorsum , gene
Abstract Our previous study has shown that anti‐Thy‐1 antibody promotes neurite outgrowth of cultured dorsal root ganglion (DRG) neurons in a protein kinase A (PKA)‐dependent manner. The present study provided another intracellular signaling pathway for the neurotrophic effect of anti‐Thy‐1 antibody. In DMSO‐treated control cells, Thy‐1 was enriched in microdomain‐like structures on cell membranes by immunofluorescence observation. Treatment of DRG neurons with anti‐Thy‐1 antibody not only stimulated neurite outgrowth, but also increased the branching complexity of the neurites in both small and large neurons. We have previously shown that anti‐Thy‐1 antibody causes a time‐dependent activation of mitogen‐activated protein kinase (MEK) and of cyclic AMP response‐element binding protein (CREB). Here, anti‐Thy‐1 antibody elicited a transient activation of c‐Src kinase, and the activation of c‐Src kinase appeared occurring upstream of the activation of MEK and CREB, since pretreatment with the Src kinase inhibitor, PP2, effectively abolished the anti‐Thy‐1 antibody‐induced neurite outgrowth and the phosphorylation of MEK and CREB. CREB phosphorylation might result in upregulation of certain neurite outgrowth‐related proteins. We therefore conclude that anti‐Thy‐1 antibody activates the c‐Src kinase‐MEK‐CREB cascade and overcomes the inhibitory effect of Thy‐1 on neurite outgrowth in DRG neurons. J. Cell. Biochem. 103: 67–77, 2008. © 2007 Wiley‐Liss, Inc.