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 Blood, 1 February 2007, Vol. 109, No. 3, pp. 862-867.
Prepublished online as a Blood First Edition Paper on October 19, 2006; DOI 10.1182/blood-2006-07-028829.

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Submitted July 11, 2006
Accepted September 17, 2006

PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase

Rebecca J. Chan and Gen-Sheng Feng*

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN
Burnham Institute for Medical Research, La Jolla, CA

* Corresponding author; email: gfeng{at}burnham.org.

Elucidation of the molecular mechanisms underlying carcinogenesis has benefited tremendously from the identification and characterization of oncogenes and tumor suppressor genes. One new advance in this field is the identification of PTPN11 as the first proto-oncogene that encodes a cytoplasmic tyrosine phosphatase with two Src-homology 2 (SH2) domains (Shp2). This tyrosine phosphatase was previously shown to play an essential role in normal hematopoiesis. More recently, somatic missense PTPN11 gain-of-function mutations have been detected in leukemias and rarely in solid tumors, and have been found to induce aberrant hyperactivation of the Ras-Erk pathway. This progress represents another milestone in the leukemia/cancer research field and provides a fresh view on molecular mechanisms underlying cell transformation.


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