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Germ-line and somatic PTPN11 mutations in human disease
Marco Tartaglia1, Bruce D Gelb
1Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. mtartaglia@iss.it
European Journal of Medical Genetics
|August 2, 2005
Summary
Gain-of-function mutations in the PTPN11 gene, encoding SHP-2 phosphatase, cause developmental disorders like Noonan syndrome and contribute to cancers. Understanding SHP-2's role in signaling is crucial for these diseases.
Area of Science:
- Molecular Biology
- Cell Signaling
- Genetics
Background:
- Protein tyrosyl phosphorylation is a key regulator of cellular responses.
- SHP-2 (protein tyrosine phosphatase) is vital for intracellular signaling, development, and hematopoiesis.
- Deregulation of signaling pathways, including SHP-2, can lead to diseases.
Purpose of the Study:
- To review the role of SHP-2 in signal transduction, development, and hematopoiesis.
- To discuss the implications of SHP-2 gain-of-function mutations in disease.
Main Methods:
- Review of existing literature on SHP-2 function and mutations.
- Analysis of germ-line and somatic mutations in the PTPN11 gene.
Main Results:
- Germ-line mutations in PTPN11 cause developmental disorders, notably Noonan syndrome.
- Somatic mutations in PTPN11 are implicated in myeloid and lymphoid malignancies.
- Gain-of-function mutations in SHP-2 disrupt normal cellular processes.
Conclusions:
- SHP-2 is a critical mediator in signaling pathways relevant to development and cancer.
- Mutations in PTPN11 highlight SHP-2's dual role in developmental disorders and malignancies.
- Further research into SHP-2 function is essential for therapeutic strategies.
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