Format

Send to

Choose Destination
Biol Chem. 2006 Jun;387(6):677-85.

Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more.

Author information

1
Department of Laboratory Medicine and Pathobiology, University of Toronto and Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.

Abstract

Serine proteinases, like trypsin, can play a hormone-like role by triggering signal transduction pathways in target cells. In many respects these hormone-like actions of proteinases can now be understood in terms of the pharmacodynamics of the G protein-coupled 'receptor' responsible for the cellular actions of thrombin (proteinase-activated receptor-1, or PAR1). PAR1, like the other three members of this receptor family (PAR2, PAR3 and PAR4), has a unique mechanism of activation involving the proteolytic unmasking of an N-terminally tethered sequence that can activate the receptor. The selective activation of each PAR by short synthetic peptides representing these sequences has demonstrated that PAR1, PAR2 and PAR4 play important roles in regulating physiological responses ranging from vasoregulation and cell growth to inflammation and nociception. We hypothesise that the tissue kallikreins may regulate signal transduction via the PARs. Although PARs can account for many of their biological actions, kallikreins may also cause effects by mechanisms not involving the PARs. For instance, trypsin activates the insulin receptor and thrombin can act via a mechanism involving its non-catalytic domains. Based on the data we summarise, we propose that the kallikreins, like thrombin and trypsin, must now be considered as important 'hormonal' regulators of tissue function.

PMID:
16800728
DOI:
10.1515/BC.2006.086
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center