A SHPing tale: perspectives on the regulation of SHP-1 and SHP-2 tyrosine phosphatases by the C-terminal tail.
Protein tyrosine phosphorylation is a ubiquitous signalling mechanism and is regulated by a balance between the action of kinases and phosphatases. The SH2 domain-containing phosphatases SHP-1 and SHP-2 are the best studied of the classical non-receptor tyrosine phosphatases, but it is intriguing that despite their close sequence and structural homology these two phosphatases play quite different cellular roles. In particular, whereas SHP-1 plays a largely negative signalling role suppressing cellular activation, SHP-2 plays a largely positive signalling role. Major sequence differences between the two molecules are apparent in the approximately 100 amino acid residues at the extreme C-terminus of the proteins, beyond the phosphatase catalytic domain. Here we review how the differences in the tails of these proteins may regulate their activities and explain some of their functional differences.
Poole
Alastair W
AW
Department of Pharmacology, University of Bristol, School of Medical Sciences, Bristol BS8 1TD, UK. a.poole@bristol.ac.uk
Jones
Matthew L
ML
D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008969:Molecular Sequence Data; D010712:Phosphatidic Acids / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; D010712:Phosphatidic Acids; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases