Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1.
Site-selective dephosphorylation of receptor tyrosine kinases contributes to receptor regulation. The receptor-like protein tyrosine phosphatase DEP-1 site-selectively dephosphorylates the PDGF beta-receptor. DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021 and the less preferred pY857 and pY562 sites was analyzed. Double substitutions of basic residues at -4 and +3 of pY857 and pY562 peptides improved affinity. Substitutions of single amino acids indicated preference for an acidic residue at position -1 and a preference against a basic residue at position +3. DEP-1 site-selective dephosphorylation of PDGF beta-receptor is thus determined by the primary sequence surrounding phosphorylation sites and involves interactions with residues spanning at least between positions -1 and +3.
Persson
Camilla
C
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Engström
Ulla
U
Mowbray
Sherry L
SL
Ostman
Arne
A
D000409:Alanine / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D020134:Catalytic Domain; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry / Q000378:metabolism*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D013379:Substrate Specificity
D010748:Phosphopeptides; D020797:Receptor, Platelet-Derived Growth Factor beta; D017027:Protein Tyrosine Phosphatases; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D008239:Lysine; D000409:Alanine