Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2

Miikka Vikkula, Laurence M. Boon, Kermit L Carraway, Jennifer T. Calvert, A. John Diamonti, Boyan Goumnerov, Krystyna A. Pasyk, Douglas A. Marchuk, Matthew L. Warman, Lewis C. Cantley, John B. Mulliken, Bjorn R. Olsen

Research output: Contribution to journalArticle

530 Citations (Scopus)

Abstract

Venous malformations (VMs), the most common errors of vascular morphogenesis in humans, are composed of dilated, serpiginous channels. The walls of the channels have a variable thickness of smooth muscle; some mural regions lack smooth muscle altogether. A missense mutation resulting in an arginine-to-tryptophan substitution at position 849 in the kinase domain of the receptor tyrosine kinase TIE2 segregates with dominantly inherited VM in two unrelated families. Using proteins expressed in insect cells, we demonstrate that the mutation results in increased activity of TIE2. We conclude that an activating mutation in TIE2 causes inherited VMs in the two families and that the TIE2 signaling pathway is critical for endothelial cell smooth muscle cell communication in venous morphogenesia.

Original languageEnglish (US)
Pages (from-to)1181-1190
Number of pages10
JournalCell
Volume87
Issue number7
DOIs
StatePublished - Dec 27 1996
Externally publishedYes

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TIE-2 Receptor
Receptor Protein-Tyrosine Kinases
Smooth Muscle
Blood Vessels
Muscle
Mutation
Critical Pathways
Missense Mutation
Morphogenesis
Cell Communication
Tryptophan
Smooth Muscle Myocytes
Insects
Arginine
Phosphotransferases
Endothelial Cells
Endothelial cells
Substitution reactions
Cells
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Vikkula, M., Boon, L. M., Carraway, K. L., Calvert, J. T., Diamonti, A. J., Goumnerov, B., ... Olsen, B. R. (1996). Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell, 87(7), 1181-1190. https://doi.org/10.1016/S0092-8674(00)81814-0

Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. / Vikkula, Miikka; Boon, Laurence M.; Carraway, Kermit L; Calvert, Jennifer T.; Diamonti, A. John; Goumnerov, Boyan; Pasyk, Krystyna A.; Marchuk, Douglas A.; Warman, Matthew L.; Cantley, Lewis C.; Mulliken, John B.; Olsen, Bjorn R.

In: Cell, Vol. 87, No. 7, 27.12.1996, p. 1181-1190.

Research output: Contribution to journalArticle

Vikkula, M, Boon, LM, Carraway, KL, Calvert, JT, Diamonti, AJ, Goumnerov, B, Pasyk, KA, Marchuk, DA, Warman, ML, Cantley, LC, Mulliken, JB & Olsen, BR 1996, 'Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2', Cell, vol. 87, no. 7, pp. 1181-1190. https://doi.org/10.1016/S0092-8674(00)81814-0
Vikkula, Miikka ; Boon, Laurence M. ; Carraway, Kermit L ; Calvert, Jennifer T. ; Diamonti, A. John ; Goumnerov, Boyan ; Pasyk, Krystyna A. ; Marchuk, Douglas A. ; Warman, Matthew L. ; Cantley, Lewis C. ; Mulliken, John B. ; Olsen, Bjorn R. / Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. In: Cell. 1996 ; Vol. 87, No. 7. pp. 1181-1190.
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