期刊
BLOOD
卷 103, 期 6, 页码 2325-2331出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-09-3287
关键词
-
类别
资金
- NCI NIH HHS [P30 CA82103, P01 CA40046, CA80916, K23 CA80915] Funding Source: Medline
- NHLBI NIH HHS [HL04409] Funding Source: Medline
- NICHD NIH HHS [HD28825] Funding Source: Medline
The PTPN11 gene encodes SHP-2 (Src homology 2 domain-containing protein tyrosine Phosphatase), a nonreceptor tyrosine protein tyrosine phosphatase (PTPase) that relays signals from activated growth factor receptors to p21(Ras), (Ras) and other signaling molecules. Mutations in PTPN11 cause Noonan syndrome (INS), a developmental disorder characterized by cardiac and skeletal defects. NS is also associated with a spectrum of hematologic disorders, including juvenile myelomonocytic leukemia (JMML). To test the hypothesis that PTPN11 mutations might contribute to myeloid leukemia mogenesis, we screened the entire coding region for mutations in 51 JMML specimens and in selected exons from 60 patients with other myeloid malignancies. Missense mutations in PTPN11 were detected in 16 of 49 JMML specimens from patients without NS, but they were less common in other myeloid malignancies. RAS, NF1, and PTPN11 mutations are largely mutually exclusive in JMML, which suggests that mutant SHP-2 proteins deregulate myeloid growth through Ras. However, although Ba/F3 cells engineered to express leukemia-associated SHP-2 proteins cells Showed enhanced growth factor-independent survival, biochemical analysis failed to demonstrate hyperactivation of the Ras effectors extra-cell cellular-regulated kinase (ERK) or Akt. We conclude that SHP-2 is an important cellular PTPase that is mutated in myeloid malignancies. Further investigation is required to clarify how these mutant proteins interact with Ras and other effectors to deregulate myeloid growth. (Blood. (C) 2004 by The American Society of Hematology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据