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Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer.
J Cell Sci. 2007 Mar 15; 120(Pt 6):921-8.JC

Abstract

Protease-activated receptors (PARs) are G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. PARs play crucial roles in hemostasis and thrombosis, as well as in inflammation and vascular development. Coagulant proteases, which are generated at sites of vascular injury, act mainly through PARs to elicit signalling in a variety of cell types. Since PARs are irreversibly activated signalling must be tightly regulated. Desensitization and trafficking of proteolytically activated PARs control the magnitude, duration and spatial aspects of receptor signalling. Recent studies have revealed novel endocytic sorting mechanisms that regulate PAR signalling. PARs have also been implicated in tumor progression. PARs are overexpressed in several types of malignant cancer, transmit signals in response to tumor-generated proteases and promote tumor growth, invasion and metastasis. Recent work also indicates that matrix metalloprotease 1 (MMP-1) signals through PAR1 to promote tumor growth and invasion. In addition to PAR overexpression, tumor cells display aberrant PAR1 trafficking, which causes persistent signalling and cellular invasion. Thus, a novel type of gain-of-function in GPCR signalling in cancer can be acquired through dysregulation of receptor trafficking.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17344429

Citation

Arora, Puneeta, et al. "Protease-activated Receptor Signalling, Endocytic Sorting and Dysregulation in Cancer." Journal of Cell Science, vol. 120, no. Pt 6, 2007, pp. 921-8.
Arora P, Ricks TK, Trejo J. Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. J Cell Sci. 2007;120(Pt 6):921-8.
Arora, P., Ricks, T. K., & Trejo, J. (2007). Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. Journal of Cell Science, 120(Pt 6), 921-8.
Arora P, Ricks TK, Trejo J. Protease-activated Receptor Signalling, Endocytic Sorting and Dysregulation in Cancer. J Cell Sci. 2007 Mar 15;120(Pt 6):921-8. PubMed PMID: 17344429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. AU - Arora,Puneeta, AU - Ricks,Tiffany K, AU - Trejo,JoAnn, PY - 2007/3/9/pubmed PY - 2007/12/6/medline PY - 2007/3/9/entrez SP - 921 EP - 8 JF - Journal of cell science JO - J Cell Sci VL - 120 IS - Pt 6 N2 - Protease-activated receptors (PARs) are G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. PARs play crucial roles in hemostasis and thrombosis, as well as in inflammation and vascular development. Coagulant proteases, which are generated at sites of vascular injury, act mainly through PARs to elicit signalling in a variety of cell types. Since PARs are irreversibly activated signalling must be tightly regulated. Desensitization and trafficking of proteolytically activated PARs control the magnitude, duration and spatial aspects of receptor signalling. Recent studies have revealed novel endocytic sorting mechanisms that regulate PAR signalling. PARs have also been implicated in tumor progression. PARs are overexpressed in several types of malignant cancer, transmit signals in response to tumor-generated proteases and promote tumor growth, invasion and metastasis. Recent work also indicates that matrix metalloprotease 1 (MMP-1) signals through PAR1 to promote tumor growth and invasion. In addition to PAR overexpression, tumor cells display aberrant PAR1 trafficking, which causes persistent signalling and cellular invasion. Thus, a novel type of gain-of-function in GPCR signalling in cancer can be acquired through dysregulation of receptor trafficking. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/17344429/Protease_activated_receptor_signalling_endocytic_sorting_and_dysregulation_in_cancer_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=17344429 DB - PRIME DP - Unbound Medicine ER -