Dimerization-induced inhibition of receptor protein tyrosine phosphatase function through an inhibitory wedge.
The function and regulation of the receptorlike transmembrane protein tyrosine phosphatases (RPTPs) are not well understood. Ligand-induced dimerization inhibited the function of the epidermal growth factor receptor (EGFR)-RPTP CD45 chimera (EGFR-CD45) in T cell signal transduction. Properties of mutated EGFR-CD45 chimeras supported a general model for the regulation of RPTPs, derived from the crystal structure of the RPTPalpha membrane-proximal phosphatase domain. The phosphatase domain apparently forms a symmetrical dimer in which the catalytic site of one molecule is blocked by specific contacts with a wedge from the other.
Majeti
R
R
Department of Microbiology, University of California, San Francisco, CA 94143, USA.
Bilwes
A M
AM
Noel
J P
JP
Hunter
T
T
Weiss
A
A
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D019281:Dimerization; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D009154:Mutation; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051746:ZAP-70 Protein-Tyrosine Kinase
D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D002118:Calcium