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KMID : 0624620080410060479
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BMB Reports
2008 Volume.41 No. 6 p.479 ~ p.484
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Transient activation of the MAP kinase signaling pathway by the forward signaling of EphA4 in PC12 cells
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Shin Jong-Dae
Gu Chang-Kyu
Kim Ji-Eun
Park Soo-Chul
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Abstract
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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. [BMB reports 2008; 41(6): 479-484]
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KEYWORD
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Endocytosis, EphA4 receptor, MAP kinase, PC12 cell
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