title: Transient activation of the MAP kinase signaling pathway by the forward signaling of EphA4 in PC12 cells.
abstract: In the present study, we demonstrate that ephrin-A5 is able to induce a transient increase of MAP kinase activity in PC12 cells. However, the effects of ephrin-A5 on the MAP kinase signaling pathway are about three-fold less than that of EGF. In addition, we demonstrate that EphA4 is the only Eph member expressed in PC12 cells, and that tyrosine phosphorylation induced by ephrin-A5 treatment is consistent with the magnitude and longevity of MAP kinase activation. Experiments using the Ras dominant negative mutant N17Ras reveal that Ras plays a pivotal role in ephrin-A5-induced MAP kinase activation in PC12 cells. Importantly, we found that the EphA4 receptor is rapidly internalized by endocytosis upon engagement of ephrin-A5, leading to a subsequent reduction in the MAP kinase activation. Together, these data suggest a novel regulatory mechanism of differential Ras-MAP kinase signaling kinetics exhibited by the forward signaling of EphA4 in PC12 cells.
authors.affiliation: The Institute of Natural Science, Sookmyung Womenos University, Seoul, Korea.
authors.forename: Jongdae
authors.initials: J
authors.lastname: Shin
authors.forename: Changkyu
authors.initials: C
authors.lastname: Gu
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Soochul
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004705:Endocytosis; D047468:Immunoprecipitation; D020935:MAP Kinase Signaling System; D016716:PC12 Cells; D051381:Rats; D036122:Receptor, EphA4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D036122:Receptor, EphA4