Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor

Caterina Bianco, Subha Kannan, Marta De Santis, Masaharu Seno, Careen K. Tang, Isabel Martinez-Lacaci, Nancy Kim, Brenda Wallace-Jones, Marc E. Lippman, Andreas D. Ebert, Christian Wechselberger, David S. Salomon

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65 Citations (Scopus)


Cripto-1 (CR-1) is a recently discovered protein of the epidermal growth factor family that fails to directly bind to any of the four known erb B type 1 receptor tyrosine kinases. The present study demonstrates that CR-1 indirectly induces tyrosine phosphorylation of erb B-4 but not of the epidermal growth factor-related receptors erb B-2 and erb B-3 in different mouse and human mammary epithelial cell lines. In addition, down-regulation of erb B-4 in NMuMG mouse mammary epithelial cells and in T47D human breast cancer cells, using an anti-orb B-4 blocking antibody or a hammerhead ribozyme vector targeted to orb B-4 mRNA, impairs the ability of CR-1 to fully activate mitogen-activated protein kinase. Finally, chemical cross- linking of 125I-CR-1 to mouse and human mammary epithelial cell membranes results in the labeling of two specific bands with a molecular weight of 130 and 60 kDa, suggesting that the CR-1 receptor represents a novel receptor structurally unrelated to any of the known type I receptor tyrosine kinases. In conclusion, these data demonstrate that CR-1, upon binding to an unknown receptor, can enhance the tyrosine kinase activity of erb B-4 and that a functional erb B-4 receptor is required for CR-1-induced MAPK activation.

Original languageEnglish
Pages (from-to)8624-8629
Number of pages6
JournalJournal of Biological Chemistry
Issue number13
Publication statusPublished - Mar 26 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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