The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling.
Src homology-2 (SH2) domain-containing phosphatases (Shps) are a small, highly conserved subfamily of protein-tyrosine phosphatases, members of which are present in both vertebrates and invertebrates. The mechanism of regulation of Shps by ligand binding is now well understood. Much is also known about the normal signaling pathways regulated by each Shp and the consequences of Shp deficiency. Recent studies have identified mutations in human Shp2 as the cause of the inherited disorder Noonan syndrome. Shp2 mutations might also contribute to the pathogenesis of some leukemias. In addition, Shp2 might be a key virulence determinant for the important human pathogen Helicobacter pylori. Despite these efforts, however, the key targets of each Shp have remained elusive. Identifying these substrates remains a major challenge for future research.
Neel
Benjamin G
BG
Cancer Biology Program Division of Hematology-Oncology Beth Israel-Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. bneel@caregroup.harvard.edu
Gu
Haihua
H
Pao
Lily
L
D000818:Animals; D001665:Binding Sites; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007938:Leukemia / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D013577:Syndrome; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; D014443:Tyrosine; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases