CD44 variant exon v5 encodes a tyrosine that is sulphated.
Functional differences between members of the CD44 family of cell surface glycoproteins is mediated in part by differential post-translational modification of these proteins and by alternative splicing. Tyrosine sulphation is a secondary modification of the primary amino acid structure of a number of secreted, transmembrane and lysosomal proteins, which is associated with promotion of protein-protein interactions. Here we identify a cannonical tyrosine-sulphation motif within rat and mouse CD44 exon v5. We show that inorganic sulphate is incorporated into the metastasis-associated rat CD44v4-v7 splice variant. The sulphate is not incorporated into sulphated glycosaminoglycan or other sugar modifications of CD44v4-v7. A point mutation of the exon v5 tyrosine to phenylalanine destroys inorganic sulphate incorporation into CD44v4-v7. These results demonstrate that the tyrosine-sulphation motif within rat CD44 exon v5 is used in vivo, and suggest that exon v5 may be involved in mediating CD44 ligand binding-activity by means of its sulphated tyrosine.
Forschungszentrum Karlsruhe, Institute of Genetics, Germany. sleeman@igen.fzk.de
J P
JP
Sleeman
U
U
Rahmsdorf
A
A
Steffen
H
H
Ponta
P
P
Herrlich
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons; D014644:Genetic Variation; D018960:Hyaluronan Receptors / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D051381:Rats; D013431:Sulfates / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000302:isolation & purification*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000302:isolation & purification
C113800:CD44v5 antigen; D018960:Hyaluronan Receptors; D010446:Peptide Fragments; D013431:Sulfates; D013463:Sulfuric Acid Esters; C005662:tyrosine O-sulfate; D014443:Tyrosine