Internalization and recycling of activated thrombin receptors

Hoxie, James A., Ahuja, Menaka, Belmonte, Elizabeth, Pizarro, Shelly, Parton, Robert and Brass, Lawrence F. (1993) Internalization and recycling of activated thrombin receptors. Journal of Biological Chemistry, 268 18: 13756-13763.

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Author Hoxie, James A.
Ahuja, Menaka
Belmonte, Elizabeth
Pizarro, Shelly
Parton, Robert
Brass, Lawrence F.
Title Internalization and recycling of activated thrombin receptors
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 1993-06
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 268
Issue 18
Start page 13756
End page 13763
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Abstract Shortly after activation by either thrombin or the tethered ligand domain peptide SFLLRN, thrombin receptors undergo homologous desensitization, temporarily losing their ability to respond to both agonists. We have examined the role of receptor internalization and recycling in this process using receptor-directed antibodies as probes. The results show within 1 min of activation >85% of the approximately 200,000 thrombin receptors on megakaryoblastic human erythroleukemia (HEL) and CHRF-288 cells are sequestered into endosomes via coated pits, after which the majority are transferred to lysosomes. This process does not require proteolysis of the receptor and occurs with sufficient speed to play a major role in the regulation of thrombin receptor function. Although most of the internalized receptors are ultimately degraded, approximately 25% return to the cell surface. These recycled receptors are in a state in which they can respond to SFLLRN but not thrombin; nor do they self-activate despite the apparent continued presence of the tethered ligand. In contrast to other G protein-coupled receptors, which are internalized and then recycled in an activatable state, recovery of the thrombin response occurs only after the expression on the cell surface of adequate numbers of newly synthesized receptors.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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