Wnt11/5a complex formation caused by tyrosine sulfation increases canonical signaling activity.
Wnt signaling plays important roles in embryonic development, tissue differentiation, and cancer. In both normal and malignant tissue, Wnt family members are often expressed combinatorially, although the significance of this is not understood. We recently showed that Wnt11 and Wnt5a are both required for the initiation of embryonic axis formation and that the two proteins physically interact with each other. However, little is known about the mechanism or biological significance of Wnt-Wnt protein interaction. Here we show in three assays, with Xenopus oocytes, mouse L cells, and human embryonic stem cells, that secreted Xenopus Wnt11/5a complexes have more canonical Wnt signaling activity than secreted Wnt11 or Wnt5a acting alone. We demonstrate that the sulfation activity of tyrosylprotein sulfotransferase-1 (TPST-1) is required for Xenopus dorsal axis formation and that O-sulfation of specific tyrosine residues is necessary for the interaction of Wnt11 with Wnt5a and for enhanced canonical signaling activity. These findings demonstrate a novel aspect of Wnt biology-Wnt family member interaction that depends on tyrosyl sulfation.
Cha
Sang-Wook
SW
Division of Developmental Biology, Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Tadjuidje
Emmanuel
E
White
Jody
J
Wells
James
J
Mayhew
Christopher
C
Wylie
Christopher
C
Heasman
Janet
J
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000071818:Wnt-5a Protein; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C085096:Wnt5a protein, Xenopus; D029867:Xenopus Proteins; C512785:wnt11b protein, Xenopus; D014443:Tyrosine