Ecto-enzymes: physiology meets pathology

Abstract

Ecto-enzymes are catalytic membrane proteins with their active sites outside the cell. They include cholinesterase, which inactivates acetylcholine, and angiotensin-converting enzyme, which converts angiotensin I to biologically active angiotensin II, and numerous other peptidases, transpeptidases, nucleotidases, phosphodiesterases, and phosphatases. Many CD antigens of leukocytes are ecto-enzymes; some CD antigens for which no function is currently known are probably ectoenzymes. Expression is highly regulated and correlated with differentiation and activation. Some are highly restricted in distribution; others are ubiquitous. Many are shared between leukocytes and non-hematogenous cells. Biological functions appear to depend on the type and location of the cell in which expression occurs, and include recycling of nutrients, local control of response to cytokines and hormones, bone formation, cell mobility, invasion, and metastasis. Many novel regulatory functions of ecto-enzymes remain to be discovered, and may reveal new mechanisms of local extracellular control of cellular function.

Binding of CD157 Protein to Fibronectin Regulates Cell Adhesion and Spreading

“…Ectoenzymes are a large and heterogeneous class of cell surface-expressed enzymes (1). Many are expressed in leukocytes and endothelial cells, where they modulate each step of leukocyte trafficking (2).…”

PC-1 Nucleoside Triphosphate Pyrophosphohydrolase Deficiency in Idiopathic Infantile Arterial Calcification

“…10,[12][13][14] PDNP family isozymes with NTPPPH activity are expressed as cell-bound class II (intracellular N-terminus) transmembrane glycoproteins of 120 to 130 kd that share a highly homologous extracellular domain containing two somatomedin B-like regions and a highly conserved catalytic site. 13,14 Furthermore, soluble enzymatically active NTPPPH species are liberated by proteolysis of the parent molecules.…”

“…10,[12][13][14] PDNP family isozymes with NTPPPH activity are expressed as cell-bound class II (intracellular N-terminus) transmembrane glycoproteins of 120 to 130 kd that share a highly homologous extracellular domain containing two somatomedin B-like regions and a highly conserved catalytic site. 13,14 Furthermore, soluble enzymatically active NTPPPH species are liberated by proteolysis of the parent molecules. 13,14 The most widely distributed PDNP family NTPPPH isozyme is plasma cell membrane glycoprotein-1 (PC-1), 10,[12][13][14] which is particularly abundant in fibroblasts, chondrocytes, osteoblasts, and hepatocytes, and also circulates in soluble form(s) in plasma.…”

“…13,14 Furthermore, soluble enzymatically active NTPPPH species are liberated by proteolysis of the parent molecules. 13,14 The most widely distributed PDNP family NTPPPH isozyme is plasma cell membrane glycoprotein-1 (PC-1), 10,[12][13][14] which is particularly abundant in fibroblasts, chondrocytes, osteoblasts, and hepatocytes, and also circulates in soluble form(s) in plasma. 15 The neural, enteric, and genitourinary tract PDNP family NTPPPH isozyme B10/PDNP3 also has been detected in a soluble form in plasma.…”

Extracellular nucleotide metabolism and signaling in the pathophysiology of articular cartilage

“…Interestingly, while NPP1 or TNAP knockout mice exhibit bone mineralization (14,96,97), the double-knockout mice are normal (98). How disruption of this balance leads to pathologic cartilage calcification is discussed below.…”