Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases.
The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and roles in a range of cellular processes, including proliferation, migration, invasion, differentiation, inflammation and angiogenesis that are required in both normal physiology as well as pathological conditions. These roles require cleavage of a range of substrates, including extracellular matrix proteins, growth factors, cytokines as well as other proteinases. In addition, it has been clear since the earliest days of KLK research that cleavage of cell surface substrates is also essential in a range of KLK-mediated cellular processes where these peptidases are essentially acting as agonists and antagonists. In this review we focus on these KLK-regulated cell surface receptor systems including bradykinin receptors, proteinase-activated receptors, as well as the plasminogen activator, ephrins and their receptors, and hepatocyte growth factor/Met receptor systems and other plasma membrane proteins. From this analysis it is clear that in many physiological and pathological settings KLKs have the potential to regulate multiple receptor systems simultaneously; an important issue when these peptidases and substrates are targeted in disease.
Ying
Y
Dong
Brittney S
BS
Harrington
Mark N
MN
Adams
Andreas
A
Wortmann
Sally-Anne
SA
Stephenson
Jessica
J
Lisle
Adrian
A
Herington
John D
JD
Hooper
Judith A
JA
Clements
D000818:Animals; D006801:Humans; D007705:Kinins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013379:Substrate Specificity; D020840:Tissue Kallikreins / Q000378:metabolism*
D007705:Kinins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D020840:Tissue Kallikreins