Functional glycosylation of human podoplanin: glycan structure of platelet aggregation-inducing factor.
Podoplanin (Aggrus) is a mucin-type sialoglycoprotein that plays a key role in tumor cell-induced platelet aggregation. Podoplanin possesses a platelet aggregation-stimulating (PLAG) domain, and Thr52 in the PLAG domain of human podoplanin is important for its activity. Endogenous or recombinant human podoplanin were purified, and total glycosylation profiles were surveyed by lectin microarray. Analyses of glycopeptides produced by Edman degradation and mass spectrometry revealed that the disialyl-corel (NeuAc alpha2-3Gal beta l-3(NeuAc alpha2-6)GalNAc alpha l-O-Thr) structure was primarily attached to a glycosylation site at residue Thr52. Sialic acid-deficient podoplanin recovered its activity after additional sialylation. These results indicated that the sialylated Corel at Thr52 is critical for podoplanin-induced platelet aggregation.
Kaneko
Mika Kato
MK
Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, C-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305 8568, Japan.
Kato
Yukinari
Y
Kameyama
Akihiko
A
Ito
Hiromi
H
Kuno
Atsushi
A
Hirabayashi
Jun
J
Kubota
Tomomi
T
Amano
Koh
K
Chiba
Yasunori
Y
Hasegawa
Yasushi
Y
Sasagawa
Isoji
I
Mishima
Kazuhiko
K
Narimatsu
Hisashi
H
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D016466:CHO Cells; D002240:Carbohydrate Sequence; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000737:chemistry; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000032:analysis; D009943:Organophosphorus Compounds / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D010974:Platelet Aggregation; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry*; D040081:Protein Array Analysis; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013912:Threonine / Q000737:chemistry; D000098853:Podoplanin
D037102:Lectins; D008562:Membrane Glycoproteins; D019158:N-Acetylneuraminic Acid; D009943:Organophosphorus Compounds; D010446:Peptide Fragments; D011134:Polysaccharides; D011994:Recombinant Proteins; D013912:Threonine; C043517:2-(4-isothiocyanatophenoxy)-1,3,2-dioxaphosphinene 2-oxide; C117468:PDPN protein, human; D000098853:Podoplanin