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Molecular and Cellular Biology, June 2005, p. 4693-4702, Vol. 25, No. 11
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.11.4693-4702.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Selective Role of a Distinct Tyrosine Residue on Tie2 in Heart Development and Early Hematopoiesis

Kazunobu Tachibana,1 Nina Jones,1 Daniel J. Dumont,2,3 Mira C. Puri,2,3 and Alan Bernstein1,4,5*

Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5,1 Division of Molecular and Cellular Biology Research, Sunnybrook and Women's Regional Cancer Centre, Toronto, Ontario, Canada M4N 3M5,2 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2M9,3 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8,4 Canadian Institutes of Health Research, 160 Elgin Street, 9th Floor, Address Locator 4809A, Ottawa, Ontario, Canada K1A 0W95

Received 21 December 2004/ Returned for modification 31 January 2005/ Accepted 2 March 2005

The development of the cardiovascular system and the development of the early hematopoietic systems are closely related, and both require signaling through the Tie2 receptor tyrosine kinase. Although endothelial cells and hematopoietic cells as well as their precursors share common gene expression patterns during development, it remains completely unknown how Tie2 signaling coordinately regulates cardiovascular development and early hematopoiesis in vivo. We show here that mice with a targeted mutation in tyrosine residue 1100 in the carboxyl-terminal tail of Tie2 display defective cardiac development and impaired hematopoietic and endothelial cell development in the paraaortic splanchnopleural mesoderm similar to that seen in Tie2-null mutant mice. Surprisingly, however, unlike Tie2-null mutant mice, mice deficient in signaling through this tyrosine residue show a normal association of perivascular cells with nascent blood vessels. These studies are the first to demonstrate the physiological importance of a single tyrosine residue in Tie2, and they suggest that multiple tyrosine residues in the receptor may coordinate cardiovascular development and early hematopoietic development.

* Corresponding author. Mailing address: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Rm. 982, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. Phone: (613) 954-1974. Fax: (613) 948-7227. E-mail: abernstein{at}cihr.gc.ca.

Molecular and Cellular Biology, June 2005, p. 4693-4702, Vol. 25, No. 11
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.11.4693-4702.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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