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Modulation of type‐1 protein phosphatase by synthetic peptides corresponding to the carboxyl terminus
Author(s) -
Martin Bruce L.,
Shriner Carol L.,
Brautigan David L.
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80712-c
Subject(s) - phosphatase , peptide , c terminus , n terminus , chemistry , okadaic acid , biochemistry , peptide sequence , stereochemistry , enzyme , amino acid , gene
Protein phosphatase type‐I (PP‐1) has a protease resistant catalytic core M r = 35000 (PP‐35K) and a carboxyl terminal segment which affects activity with various substrates. We found that micromolar concentration of a synthetic peptide, corresponding to residues 312–326 of the PP‐1 carboxyl terminus (P312‐326) that is missing from PP‐35K, increased the phosphatase activity of PP‐35K with phosphorylase and myosin light chains as substrates by decreasing the apparent K m without a change in V m . Purified PP‐1 and PP‐35K were inhibited identically by okadaic acid, but peptide P312‐326 only stimulated the activity of PP‐35K, not full‐length PP‐1. Other peptides corresponding to the carboxyl terminus of phosphatase‐2A or to the amino terminus of PP‐1 did not affect the activity of PP‐35K. A sequence conserved in PP‐1 from different species, Pro‐He‐Thr‐Pro‐Pro was implicated as the active region because a derivative peptide, Ala‐Pro‐Ile‐Thr‐Pro‐Pro‐Ala, stimulated the activity of PP‐35K to the same extent as peptide P312‐326 although at higher concentrations. These results indicate that the carboxyl terminus of PP‐1 interacts with the catalytic core to modulate its activity, and suggest that the physiological regulation of PP‐1 may involve this segment.