These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion cells.
    Author: Cheng Q, Sasaki Y, Shoji M, Sugiyama Y, Tanaka H, Nakayama T, Mizuki N, Nakamura F, Takei K, Goshima Y.
    Journal: Mol Cell Neurosci; 2003 Nov; 24(3):632-45. PubMed ID: 14664814.
    Abstract:
    Ephrin-As are repulsive axonal guidance cues that regulate retinotectal projection. EphA tyrosine kinases, which are the receptors of ephrin-As, activate signaling cascades leading to cytosckeleton reorganization. Here, we address the role of cyclin-dependent kinase (Cdk) 5 in Eph receptor signaling induced by ephrin-A5. Ephrin-A5 induced a cell morphological response in PC-3M cells that endogenously express Cdk5 and EphA2, a receptor for ephrin-A5. This response was augmented by the transfection of p35, which is a neuronal regulator of Cdk5. While the morphological response of native PC-3M cells was not affected by olomoucine, an inhibitor of Cdk, the response was inhibited in the p35-transfected cells. In retinal ganglion cells, either olomoucine at 20 microM or Y-27632 at 10 microM, an inhibitor of Rho-kinase/ROKalpha/ROCKII, showed maximum inhibitory effect against ephrin-A5 (10 microg/ml)-induced growth cone collapse. Combined application of olomoucine and Y-27632 further suppressed the ephrin-A5-induced response. Ephrin-A5 evoked phosphorylation of Cdk5 at Tyr15 and tau, a substrate of Cdk5 in retinal growth cones. Recombinant herpes simplex virus expressing Cdk5 mutant (kinase-negative or Tyr15 to Ala) showed a dominant-negative effect on the ephrin-A5-induced growth cone collapse. These findings demonstrate that both Cdk5 and the Rho kinase pathway independently contribute to the downstream of ephrin-A-induced signaling in retinal ganglion cells.
    [Abstract] [Full Text] [Related] [New Search]