ADAM19 autolysis is activated by LPS and promotes non-classical secretion of cysteine-rich protein 2.
ADAM family proteins are type I transmembrane, zinc-dependent metalloproteases. This family has multiple conserved domains, including a signal peptide, a pro-domain, a metalloprotease domain, a disintegrin (DI) domain, a cysteine-rich (Cys) domain, an EGF-like domain, a transmembrane domain, and a cytoplasmic domain. The Cys and DI domains may play active roles in regulating proteolytic activity or substrate specificity. ADAM19 has an autolytic processing activity within its Cys domain, and the processing is necessary for its proteolytic activity. To identify a new physiological function of ADAM19, we screened for associating proteins by using the extracellular domain of ADAM19 in a yeast two-hybrid system. Cysteine-rich protein 2 (CRIP2) showed an association with ADAM19 through its DI and Cys domains. Sequence analysis revealed that CRIP2 is a secretable protein without a classical signal. CRIP2 secretion was increased by overexpression of ADAM19 and decreased by suppression of ADAM19 expression. Moreover, CRIP2 secretion increased in parallel with the autolytic processing of ADAM19 stimulated by lipopolysaccharide. These findings suggest that ADAM19 autolysis is activated by lipopolysaccharide and that ADAM19 promotes the secretion of CRIP2.
Tanabe
Chiaki
C
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Hotoda
Nika
N
Sasagawa
Noboru
N
Futai
Eugene
E
Komano
Hiroto
H
Ishiura
Shoichi
S
D051722:ADAM Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D006801:Humans; D060588:LIM Domain Proteins; D008070:Lipopolysaccharides / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; C486176:CRIP2 protein, human; D060588:LIM Domain Proteins; D008070:Lipopolysaccharides; D051722:ADAM Proteins; C411902:ADAM19 protein, human