The role of cathepsin X in cell signaling.
Cathepsin X is a lysosomal cysteine protease, found predominantly in cells of monocyte/macrophage lineage. It acts as a monocarboxypepidase and has a strict positional and narrower substrate specificity relative to the other human cathepsins. In our recent studies we identified-beta(2) subunit of integrin receptors and alpha and gamma enolase as possible substrates for cathepsin X carboxypeptidase activity. In both cases cathepsin X is capable to cleave regulatory motifs at C-terminus affecting the function of targeted molecules. We demonstrated that via activation of beta(2) integrin receptor Mac-1 (CD11b/CD18) active cathepsin X enhances adhesion of monocytes/macrophages to fibrinogen and regulates the phagocytosis. By activation of Mac-1 receptor cathepsin X may regulate also the maturation of dendritic cells, a process, which is crucial in the initiation of adaptive immunity. Cathepsin X activates also the other beta(2) integrin receptor, LFA-1 (CD11a/CD18) which is involved in the proliferation of T lymphocytes. By modulating the activity of LFA-1 cathepsin X causes cytoskeletal rearrangements and morphological changes of T lymphocytes enhancing ameboid-like migration in 2-D and 3-D barriers and increasing homotypic aggregation. The cleavage of C-terminal amino acids of alpha and gamma enolase by cathepsin X abolishes their neurotrophic activity affecting neuronal cell survival and neuritogenesis.
Kos
Janko
J
University of Ljubljana, Slovenia. janko.kos@ffa.uni-lj.si
Jevnikar
Zala
Z
Obermajer
Natasa
N
D056657:Cathepsin K; D002403:Cathepsins / Q000502:physiology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D016177:Macrophage-1 Antigen; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K