Activators of protein kinase C stimulate association of Shc and the PEST tyrosine phosphatase.

Using the yeast two-hybrid system, complementary DNA clones were isolated from a HeLa cell library encoding proteins that interacted with p52shc. One of these clones encoded the non-catalytic, COOH-terminal half of the cytosolic protein tyrosine phosphatase PTP-PEST. Expression of truncated forms of p52shc in the two-hybrid system revealed that the ...
amino-terminal half of p52shc was sufficient for interaction with PTP-PEST. The p52 and p66 forms of Shc, but not the p46 form, bound to a glutathione S-transferase fusion protein containing the region of PTP-PEST isolated from the two-hybrid screen. Similarly, when HeLa cell lysates were immunoprecipitated with PTP-PEST antiserum, p52shc and p66shc proteins, but not p46shc, co-precipitated. Shc-PTP-PEST complex formation was stimulated 6-8-fold by the protein kinase C activator phorbol 12-myristate 13-acetate, while epidermal growth factor and serum had no effect. Phorbol 12-myristate 13-acetate also stimulated phosphorylation of p52shc and p66shc. The muscarinic agonist carbachol (also an activator of protein kinase C) stimulated complex formation 3-5-fold in SH-SY5Y neuroblastoma cells. These results suggest a role for PTP-PEST in G protein receptor signaling and in cross-talk between G protein receptor and tyrosine kinase receptor pathways.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Carbachol, Cell Division, Enzyme Activation, GTP-Binding Proteins, Glutathione Transferase, Hela Cells, Humans, Peptide Fragments, Phosphorylation, Protein Binding, Protein Kinase C, Protein Tyrosine Phosphatase, Non-Receptor Type 12, Protein Tyrosine Phosphatases, Proteins, Receptor Protein-Tyrosine Kinases, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Shc Signaling Adaptor Proteins, Signal Transduction, Tetradecanoylphorbol Acetate
J. Biol. Chem.
Date: Oct. 14, 1994
Download Curated Data For This Publication
9049
Switch View:
  • Interactions 3