title: Germ-line and somatic PTPN11 mutations in human disease.
abstract: Reversible protein tyrosyl phosphorylation of cell surface receptors and downstream intracellular transducers is a major regulatory mechanism used to modulate cellular responses to extracellular stimuli, and its deregulation frequently drives aberrant cell proliferation, survival and/or differentiation. SHP-2 is a cytoplasmic Src-homology 2 domain-containing protein tyrosine phosphatase that plays an important role in intracellular signaling and is required during development and hematopoiesis. Germ-line missense mutations in PTPN11, the gene coding SHP-2, have been discovered as a major molecular event underlying Noonan syndrome, an autosomal dominant trait characterized by short stature, dysmorphic facies, and congenital heart defects, as well as in other closely related developmental disorders. More recently, a distinct class of missense mutations in the same gene has been identified to occur as a somatic event contributing to myeloid and lymphoid malignancies. This review focuses on the role of SHP-2 in signal transduction, development and hematopoiesis, as well as on the consequences of SHP-2 gain-of-function.
authors.affiliation: Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. mtartaglia@iss.it
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
mesh_terms: D000818:Animals; D002648:Child; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D007938:Leukemia / Q000201:enzymology / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008958:Models, Molecular; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000201:enzymology / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse