Protein ectodomain shedding

Robert S, Maillet M, Morel E, et al. Regulation of the amyloid precursor protein ectodomain shedding by the 5-HT4 receptor and Epac. FEBS Lett 2005 579 1136-1142. 

B, Identification of the TNFa Convertase Suggests that Metalloprotease-Disintegrins Play a Role in Protein Ectodomain Shedding... 

IX. DO OTHER METALLOPROTEASE-DISINTEGRINS ALSO MEDIATE PROTEIN ECTODOMAIN SHEDDING ... 

Fig. 1.2 A scheme of the activation of ADAMs and of the shedding process. The dimeric ADAM proteases and their substrates are anchored in the membrane, but are separated from each other. Upon activation (via protein kinases ), the protease is disengaged from disintegrin and associates with the substrate. Proteolysis takes place and the free, soluble ectodomains of membrane-anchored cell-surface proteins are shed from the membrane-anchored substrates and released. (Reproduced from ref. 3, with permission of the authors and Science.)...

J. Arribas, F. Lopez Casillas, and J. Massague. Role of the juxtamembrane domains of the transforming growth factor-alpha precursor and the beta-amyloid precursor protein in regulated ectodomain shedding. 

Arribas, J., Goodly, L., Vollmer, P., Kishimoto, T.K., Rose-John, S., and Massague, J. (1996). Diverse cell surface protein ectodomains are shed by a system sensitive to metalloprotease inhibitors. J. Biol. Chem. 277 11376-11382. 

Figure 5 Proteolytic processing and signaling of the Notch receptor. In the ER, Notch is cleaved at SI by a furin-like protease to produce a stable heterodimeric receptor that is trafficked to the cell surface. Interaction with ligands such as the proteins Delta and Jagged triggers a shedding of the ectodomain by membrane-tethered metalloprotease-mediated cleavage at S2. The remnant then is cleaved at least twice, at the S3 and S4 sites, to release the Notch counterpart of Ap (Np) and the intracellular domain (NICD). The latter translocates to the nucleus where it interacts with transcription factors to influence gene expression relevant to cell differentiation.

Kidney injury molecule 1 (KlM-1) is a type 1 transmembrane protein with an immunoglobulin and mucin domain. The KlM-1 ectodomain is cleaved, shed from cells, detectable in urine, and reflects renal damage [298]. The cleavage of KlM-1 is mediated by ERK activation and is accelerated by p38 MAP kinase activation [299]. KlM-1 is not expressed in the normal kidney but is markedly up-regulated in renal proximal tubule cells by stimuli that promote dedifferentiation, including ischemic and toxic [300,301] injury. Because it is expressed in proliferating and dedifferentiated... 

KIM-1 is a type I cell membrane glycoprotein which contains, in its extracellular portion, a six-cysteine immunoglobulin-like domain, two N-glycosylation sites, and a T/SP-rich domain characteristic of mucin-like O-glycosylated proteins. The ectodomain of KlM-1 is shed from cells in vitro and in vivo into the urine in rodents and humans after proximal tubular kidney injury or in patients with renal cell carcinoma. KlM-1 confers on epithelial cells the ability to recognize and phagocytose dead cells that are present in the postischemic kidney and contribute to the obstmction of the tubule lumen that characterizes acute kidney injiuy. In... 

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