Proteolytic signals in the primary structure of annexins.
Annexins are a superfamily of calcium-dependent membrane-associated proteins which interact with phospholipids. The primary structure of Annexins I, III, VII, VIII and XI contain a region enriched in proline, glutamate, serine and threonine (PEST sequences) towards the N-terminal end while annexins II, V and VI possess PEST regions somewhat distal to the N-terminus. These PEST sequences are believed to be the signals for rapid intracellular degradation. Annexin I is known to be cleaved by calpain near its PEST region suggesting that its PEST region might be a possible calpain recognition site. Western blot analysis of annexins V and XI in rat lung homogenates suggest that these proteins are resistant to proteolysis by calpain. Annexin V was found to be stable to intrinsic lung proteases in the presence of either Ca2+ or EGTA while annexin XI was found to be partially degraded by intrinsic lung proteases in the presence of EGTA. Eight of the 10 known mammalian annexins also contain a pentapeptide sequence that is biochemically related to the KFERQ motif which is a known signal that targets protein for lysosomal proteolysis. Our data suggest that the annexins may be regulated by limited proteolysis, most likely at their N-terminal end, while most, if not all, of them might be degraded by the lysosomal pathway.
Barnes
Junor A
JA
Biochemistry Unit, Faculty of Medical Sciences, The University of West Indies, St. Augustine, Trinidad and Tobago. jbarnes@acarib-link.net
Gomes
Aldrin V
AV
D000595:Amino Acid Sequence; D000818:Animals; D017302:Annexins / Q000737:chemistry* / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
D017302:Annexins; D010446:Peptide Fragments; D010743:Phospholipids; D002154:Calpain; D002118:Calcium