Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The L1 adhesion molecule plays an important role in axon guidance and cell migration in the nervous system. L1 is also expressed by many human carcinomas. In addition to cell surface expression, the L1 ectodomain can be released by a metalloproteinase, but the biological function of this process is unknown. Here we demonstrate that membrane-proximal cleavage of L1 can be detected in tumors and in the developing mouse brain. The shedding of L1 involved a disintegrin and metalloproteinase (ADAM)10, as transfection with dominant-negative ADAM10 completely abolishes L1 release. L1-transfected CHO cells (L1-CHO) showed enhanced haptotactic migration on fibronectin and laminin, which was blocked by antibodies to alpha v beta 5 and L1. Migration of L1-CHO cells, but not the basal migration of CHO cells, was blocked by a metalloproteinase inhibitor, indicating a role for L1 shedding in the migration process. CHO and metalloproteinase-inhibited L1-CHO cells were stimulated to migrate by soluble L1-Fc protein. The induction of migration was blocked by alpha v beta 5-specific antibodies and required Arg-Gly-Asp sites in L1. A 150-kD L1 fragment released by plasmin could also stimulate CHO cell migration. We propose that ectodomain-released L1 promotes migration by autocrine/paracrine stimulation via alpha v beta 5. This regulatory loop could be relevant for migratory processes under physiological and pathophysiological conditions.
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PMID:Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. 1170 54

Epithelial (E)-cadherin is a homophilic adhesion molecule which is responsible for maintenance of baso-lateral cell adhesion and polarity. E-cadherin can be lost from the cell surface by proteolytic cleavage, resulting in the generation of an 80kDa fragment referred to a soluble E-cadherin (sE-cad). Although originally discovered in the conditioned media of breast cancer cells and later verified in the fluids of cancer patients, today sE-cad has been reported in patients with viral and bacterial infections, organ failure, and benign disease. The proteases implicated in this cleavage event include members of the disintegrin family (ADAM10 and 15), bacterial proteases (gingipains and BFT), cathepsins (B, L, S), matrix metalloproteases (MMP-2, 3, 7, 9, and 14), Kallikrein-7 (KLK7), and plasmin. Stimulus that induces sE-cad generation by ADAMs, MMPs, KLK7, and plasmin in vitro ranges from serum withdrawal to pro-inflammatory cytokines to growth factors. The cellular or physiologic consequences of sE-cad accumulation include the disruption of adherens junctions, cellular migration and invasion, induction of MMPs, as well as cell signaling, suggesting that sE-cad may contribute to disease progression.
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PMID:Soluble E-cadherin: more than a symptom of disease. 2220 48