Identification of human endomucin-1 and -2 as membrane-bound O-sialoglycoproteins with anti-adhesive activity.
Using a signal sequence trap method and database search, we identified a series of human cDNAs encoding two structurally related type I membrane proteins of approximately 25 kDa with multiple glycosylation motifs. These genes, termed endomucin-1/-2, are expressed in several human tissues including heart, kidney, and lung. Exogenously expressed human endomucin-1/-2 proteins were modified into 80-120 kDa glycoproteins, which were susceptible to O-sialoglycoprotein endopeptidase digestion. Transient overexpression of endomucin-1/-2 reduced the number of adhesion plaques and reduced cell attachment to the substrate. This phenotype was suppressed by laminin or the protein kinase inhibitor staurosporine. Our findings suggest that human endomucin-1/-2 negatively regulate cell adhesion to the extracellular matrix.
Kinoshita
M
M
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida Konoe, Japan.
Nakamura
T
T
Ihara
M
M
Haraguchi
T
T
Hiraoka
Y
Y
Tashiro
K
K
Noda
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012795:Sialoglycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052116:Sialomucins; D019311:Staurosporine / Q000494:pharmacology
D018076:DNA, Complementary; C431275:EMCN protein, human; C498985:Emcn protein, mouse; D016326:Extracellular Matrix Proteins; D009077:Mucins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; D052116:Sialomucins; D019311:Staurosporine