Endopeptidase-24.11 cleaves a chemotactic factor from alpha-calcitonin gene-related peptide.
The sequence of rat alpha-calcitonin gene-related peptide (CGRP-alpha) contains the tetrapeptide eosinophil granulocyte chemotactic factor Val32-Gly-Ser-Glu35. Peptide fragments formed following hydrolysis of rat CGRP-alpha in vitro by endopeptidase-24.11 were identified. The tetrapeptide fragment was generated following cleavage at a substrate recognition site unusual for this enzyme (-Glu-Ala-). Chemotactic activity of rat CGRP-alpha was increased following hydrolysis. Furthermore, rat CGRP-beta, which lacks the tetrapeptide sequence and is completely devoid of chemotactic activity, displayed low but measurable activity after hydrolysis. Val-Gly-Ser-Glu was identified as the principle fragment with chemotactic activity in rat CGRP-alpha. The results show that the chemotactic activity of the neuropeptide rat CGRP-alpha towards eosinophil polymorphonuclear leukocytes is increased following its hydrolysis in vitro by endopeptidase 24.11 through the formation of a previously identified eosinophil chemotactic tetrapeptide.
Davies
D
D
Department of Zoology, University of Bristol, U.K.
Medeiros
M S
MS
Keen
J
J
Turner
A J
AJ
Haynes
L W
LW
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism*; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D006868:Hydrolysis; D016209:Interleukin-8 / Q000378:metabolism; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats
D002630:Chemotactic Factors; D002631:Chemotactic Factors, Eosinophil; D006020:Glycopeptides; D016209:Interleukin-8; D010446:Peptide Fragments; D015260:Neprilysin; D015740:Calcitonin Gene-Related Peptide; C008890:phosphoramidon