Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes.

A disintegrin and metalloproteinases (ADAMs) are transmembrane proteases that cleave other proteins close to the surface in a process called shedding. The prominent member ADAM10 has been linked to several pathologies such as Alzheimer's disease, bacterial infection, cancer development and metastasis. Although the regulation of the ADAM10 activity by calcium influx and calmodulin inhibition has been reported, the spatiotemporal regulation of Ca-dependent ADAM10 activation and the required source of Ca ions have not been thoroughly studied.

Extracellular Release of a Disintegrin and Metalloproteinase Correlates With Periodontal Disease Severity.

Aim: Periodontal disease is driven by oral pathogens, including Porphyromonas gingivalis, and the release of inflammatory cytokines. These cytokines (e.g.

A jack of all trades - ADAM8 as a signaling hub in inflammation and cancer.

As a member of the family of A Disintegrin And Metalloproteinases (ADAM) ADAM8 is preferentially expressed in lymphatic organs, immune cells, and tumor cells. The substrate spectrum for ADAM8 proteolytic activity is not exclusive but is related to effectors of inflammation and signaling in the tumor microenvironment. In addition, complexes of ADAM8 with extracellular binding partners such as integrin β-1 cause an extensive intracellular signaling in tumor cells, thereby activating kinase pathways with STAT3, ERK1/2, and Akt signaling, which causes increased cell survival and enhanced motility.