SHIH-HUNG YANGChen Y.-J.Tung P.-Y.Lai W.-L.Chen Y.Jeng C.-J.Wang S.-M.2020-03-172020-03-1720080730-2312https://www.scopus.com/inward/record.uri?eid=2-s2.0-38149004162&doi=10.1002%2fjcb.21387&partnerID=40&md5=9e5fc1c6539ca7b43315934f1c08bf0ahttps://scholars.lib.ntu.edu.tw/handle/123456789/476352Our 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. © 2007 Wiley-Liss, Inc.journal article10.1002/jcb.21387174865862-s2.0-38149004162