Phosphorylation at threonine-654 is not required for negative regulation of the epidermal growth factor receptor by non-phorbol tumor promoters

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.3.812· OSTI ID:5037336

Friedman, B; Rosner, M R ^[1]; Fujiki, Hirota ^[2]

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1. Massachusetts Institute of Technology, Cambridge (USA)
2. National Cancer Center Research Institute, Tokyo (Japan)

Phosphorylation of the epidermal growth factor (EGF) receptor following activation of protein kinase C appears to negatively regulate EGF binding and the receptor-associated tyrosine kinase activity. The authors have identified two agents, the calcium ionophore A23187 and the non-phorbol tumor promoter thapsigargin, that similarly inhibit the EGF receptor binding and kinase activities through protein kinase C-independent pathways. Both agents activate protein kinases that phosphorylate the EGF receptor in A431 cells. To test the hypothesis that negative regulation of the EGF receptor always occurs through phosphorylation of threonine-654, a site uniquely phosphorylated by protein kinase C, they analyzed the tryptic phosphopeptides of EGF receptors isolated from cells treated with these agents. While limited phosphorylation of threonine-654 results from the A23187 treatment, no significant phosphorylation of this residue is detected after thapsigargin treatment. These results suggest that EGF receptor phosphorylation is a general mechanism for altering receptor properties and that site(s) of phosphorylation other than threonine-654 may negatively regulate the kinase activity as well as the binding of the EGF receptor.

• OSTI ID: 5037336
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:3; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL EFFECTS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
GROWTH FACTORS
HYDROXY ACIDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROMOTERS
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
THREONINE
TRACER TECHNIQUES
TRANSFERASES
TUMOR PROMOTERS