Putative kallikrein substrates and their (patho)biological functions.
Human tissue kallikreins (KLKs) represent the largest contiguous group of protease genes within our genome. All 15 KLK genes co-localize within approximately 260 kb in human chromosome 19q13.3-13.4 (14 640 kb→274 990 kb). They are widely expressed in several tissues and mediate a wide range of critical physiological and pathological processes. Despite the recent developments in KLK research, elucidation of their physiological substrate repertoires remains a largely unfulfilled goal. Phage display, positional scanning and combinatorial peptide library screens have provided some valuable insights into the preferred specificities of these powerful enzymes. More recently, advances in proteomic technologies have enabled more systemic approaches towards identification of KLK substrates in a physiological setting. The advent of degradomic technologies has brought to light several putative physiological substrates and has allowed a deeper appreciation of the in vivo functional roles of KLKs. The aim of this review is to provide an overview of the different techniques that have been utilized towards the elucidation of the substrate specificities of these enzymes and elaborate on their emerging in vivo substrates.
Yijing
Y
Yu
Ioannis
I
Prassas
Eleftherios P
EP
Diamandis
D006801:Humans; D007113:Immunity, Innate; D007610:Kallikreins / Q000378:metabolism*; D008954:Models, Biological; D040901:Proteomics; D011956:Receptors, Cell Surface / Q000378:metabolism; D013379:Substrate Specificity
D011956:Receptors, Cell Surface; D007610:Kallikreins