Title : Phosphorylation and O-glycosylation
sites of human
chromogranin A (
CGA79-439 ) from urine of patients with carcinoid tumors
Abstract :
- Because of their water-soluble properties, chromogranins (CGs) and chromogranin-derived fragments are released together with catecholamines from adrenal chromaffin cells during stress situations and can be detected in the blood by radiochemical and enzyme assays
- It is well known that chromogranins can serve as immunocytochemical markers for neuroendocrine tissues and as a diagnostic tool for neuroendocrine tumors
- In 1993, large CGA-derived fragments have been shown to be excreted into the urine in patients with carcinoid tumors and the present study deals with the characterization of the post-translational modifications (phosphorylation and O-glycosylation) located along the largest natural CGA-derived fragment CGA79-439
- Using mild proteolysis of peptidic material, high performance liquid chromatography, sequencing, and mass spectrometry analysis, six post-translational modifications were detected along the C-terminal CGA-derived fragment CGA79-439
- Three O-linked glycosylation sites were located in the core of the protein on Thr163, Thr165, and Thr233 , consisting in di-, tri-, and tetrasaccharides
- Three phosphorylation sites were located in the middle and C-terminal domain , on serine residues Ser200, Ser252, and Ser315
- These modified sites were compared with sequences of others species and discussed in relation with the post-translational modifications that we have reported previously for bovine CGA