Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors.
The mechanism by which thrombin induces neurite retraction was studied in NB2a mouse neuroblastoma cells. The rapid effect of thrombin (completed within minutes) appears to involve an interaction between its anion-binding exosite and the thrombin receptor. Structural alterations of this site increase the EC50 for thrombin-mediated retraction, and a hirudin C-terminal peptide that blocks this site inhibits the response. The thrombin effect was mimicked by a 14 amino acid peptide starting with Ser-42, at the proposed cleavage site of the human thrombin receptor. The protein kinase inhibitors staurosporine and H-7 blocked thrombin-induced retraction. It is therefore proposed that thrombin-mediated neurite retraction is caused by cleavage-induced activation of the thrombin receptor and involves stimulation of a protein kinase(s).
Suidan
H S
HS
Friedrich Miescher-Institut, Basel, Switzerland.
Stone
S R
SR
Hemmings
B A
BA
Monard
D
D
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009447:Neuroblastoma / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018179:Receptors, Thrombin; D019311:Staurosporine; D013917:Thrombin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
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