Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III.
Microheterogeneity of connective tissue activation peptide III (CTAP-III) was revealed by preparative and analytical isoelectric focusing. Proteolytic activities in human platelet preparations resulted in four cleavage products of platelet-derived CTAP-III. Three isoforms (CTAP-III des 1-13, des 1-14, and des 1-15/NAP-2) stimulate [14C]glycosaminoglycan synthesis; two isoforms also promote [3H]DNA synthesis in human fibroblast cultures. Elastase (from porcine pancreas) cleavage of human platelet-derived CTAP-III and rCTAP-III-Leu-21 to the des 1-15 isoforms was associated with either preservation of specific anabolic biologic activity or an actual increase in specific activity. Nonenzymatic glycosylation of lysyl residues and deamination of the NH2-terminal asparagine of platelet-derived CTAP-III were commonly present, but did not correlate with the biologic activities that were measured. Protein sequence homology shows CTAP-III and its isoforms to be members of a family of proteins (including NAP-1/II-8, MGSA, and platelet factor-4) known to be associated with growth, wound repair, inflammation, and neoplasia. The consequences of proteolytic processing reported here for CTAP-III may be characteristic of the other proteins in this group.
Rackham Arthritis Research Unit, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0531.
C W
CW
Castor
D A
DA
Walz
P H
PH
Johnson
P A
PA
Hossler
E M
EM
Smith
M C
MC
Bignall
B P
BP
Aaron
P
P
Underhill
J M
JM
Lazar
D H
DH
Hudson
D000595:Amino Acid Sequence; D001779:Blood Coagulation Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D002846:Chromatography, Affinity; D003238:Connective Tissue / Q000378:metabolism*; D005947:Glucose / Q000032:analysis; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D007525:Isoelectric Focusing; D007700:Kinetics; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000378:metabolism; D010455:Peptides; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D012689:Sequence Homology, Nucleic Acid
D001779:Blood Coagulation Factors; D010455:Peptides; C009862:connective tissue-activating peptide; C018329:low affinity platelet factor 4; D010196:Pancreatic Elastase; D005947:Glucose