PubMed · 13189873
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
W TOLCKMITT. 1954. [Gastric cathepsin].. https://pubmed.ncbi.nlm.nih.gov/13189873/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Secreted lysosomal cysteine proteases (cathepsins) are involved in degradation and remodeling of the extracellular matrix, thus contributing to cell adhesion and migration. Among the eleven human lysosomal cysteine proteases, only procathepsin X contains an RGD motif located in a highly exposed region of the propeptide, which may allow binding of the proenzyme to RGD-recognizing integrins. Here, we have tested procathepsin X for cell-adhesive properties and found that it supports integrin alpha(v)beta(3)-dependent attachment and spreading of human umbilical vein endothelial cells. Using site-directed mutants of procathepsin X, we proved that this effect is mediated by the RGD sequence within the proregion of the protease. Endogenous procathepsin X is transported to the plasma membrane, accumulates in vesicles at lamellipodia of the human umbilical vein endothelial cell, and is partly associated with the cell surface, as shown by immunofluorescence. In addition, procathepsin X is partly co-localized with integrin beta(3), as detected by immunogold electron microscopy. A direct interaction between endogenous procathepsin X and alpha(v)beta(3) was demonstrated by co-immunoprecipitation. Moreover, surface plasmon resonance analysis revealed significant and RGD-dependent binding of procathepsin X to integrin alpha(v)beta(3). Our results provide for the first time evidence that the extracellular function of cathepsin X may include binding to integrins thereby modulating the attachment of migrating cells to ECM components.
Cleavage of the fibrillar collagens occurs during physiological conditions, as well as pathological conditions. The resistance of the fibrillar collagens to degradation is due to their rigid and compact structures. There are only a limited number of proteinases that have the capability to initiate the cleavage of the fibrillar collagens. These include some of the matrix metalloproteinases (MMPs) and cathepsins, as well as a few serine proteinases. The MMPs have long been implicated in the collagen degradation and remodeling that occurs at physiological pHs. The cathepsins, on the other hand, have been implicated in the collagen cleavage that occurs at acidic pHs, particularly the collagen degradation that is mediated by osteoclasts. In addition to the MMPs, a few serine proteinases have been implicated in the collagen degradation that occurs at neutral pH. The characteristics that contribute to the resistance of the fibrillar collagens to cleavage are discussed along with the MMPs, cathepsins, and serine proteinases that can cleave these collagens.
Peptide dendrimers have a variety of applications in biology such as the vehicles for drug and gene delivery, molecular inhibitors, protein mimics, and synthetic vaccines. The multiple antigenic peptide (MAP) system is a well-known example of a discrete, dendrimeric scaffold. We explored a novel application of the MAP-based scaffold by designing molecular probes that fluoresce only after enzymatic treatment. The probes, which were synthesized on solid support, incorporate a cathepsin S dipeptide substrate (Leu-Arg), and a poly(ethylene glycol) (PEG) chain in their dendritic arms. The fluorescence emission of the near-infrared fluorochromes attached to the N-termini of the dendritic arms was quenched. Mechanistic studies revealed formation of H-type dye aggregates within the tetravalent MAP system. By varying the length of the PEG chain, three probes were synthesized, CyPEG-1, CyPEG-2, and CyPEG-3 with 4, 8, and 12 ethylene oxide units, respectively. CyPEG-2 showed optimum aqueous solubility and quenching efficiency for imaging applications. Upon proteolytic activation with cathepsin S (EC 3.4.22.27), CyPEG-2 showed greater than 70-fold increase and more than 95% recovery in fluorescence emission.