Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca sup 2+ /calmodulin-dependent protein kinase II

Gandy, S; Czernik, A J; Greengard, P

doi:10.1073/pnas.85.16.6218

Title: Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca sup 2+ /calmodulin-dependent protein kinase II

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Abstract

The amino acid sequence of the Alzheimer disease amyloid precursor (ADAP) has been deduced from the corresponding cDNA, and hydropathy analysis of the sequence suggest a receptor-like structure with a single transmembrane domain. The putative cytoplasmic domain of ADAP contains potential sites for serine and threonine phosphorylation. In the present study, synthetic peptides derived from this domain were used as model substrates for various purified protein kinases. Protein kinase C rapidly catalyzed the phosphorylation of a peptide corresponding to amino acid residues 645-661 of ADAP. Ca{sup 2+}/calmodulin-dependent protein kinase II phosphorylated ADAP peptide (645-661) on Thr-654 and Ser-655. Using rat cerebral cortex synaptosomes prelabeled with {sup 32}P{sub i}, a {sup 32}P-labeled phosphoprotein of {approx}135 kDa was immunoprecipitated by using antisera prepared against ADAP peptide(597-624), consistent with the possibility that the holoform of ADAP in rat brain is a phosphoprotein. Based on analogy with the effect of phosphorylation by protein kinase C of juxtamembrane residues in the cytoplasmic domain of the epidermal growth factor receptor and the interleukin 2 receptor, phosphorylation of ADAP may target it for internalization.

Authors:

Gandy, S; Czernik, A J; Greengard, P ^[1]

Rockefeller Univ., New York, NY (USA)

Publication Date:: Mon Aug 01 00:00:00 EDT 1988

OSTI Identifier:: 5405760

Resource Type:: Journal Article

Journal Name:: Proceedings of the National Academy of Sciences of the United States of America; (USA)

Additional Journal Information:: Journal Volume: 85:16; Journal ID: ISSN 0027-8424

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; NERVOUS SYSTEM DISEASES; PATHOGENESIS; PEPTIDES; AMINO ACID SEQUENCE; PHOSPHOTRANSFERASES; BIOCHEMISTRY; ADULTS; AGE DEPENDENCE; BRAIN; INFANTS; PHOSPHORUS 32; PHOSPHORYLATION; RATS; RECEPTORS; SERINE; SUBSTRATES; THREONINE; AGE GROUPS; AMINO ACIDS; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BODY; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; CHEMICAL REACTIONS; CHEMISTRY; CHILDREN; DAYS LIVING RADIOISOTOPES; DISEASES; ENZYMES; HYDROXY ACIDS; ISOTOPES; LIGHT NUCLEI; MAMMALS; MEMBRANE PROTEINS; MOLECULAR STRUCTURE; NERVOUS SYSTEM; NUCLEI; ODD-ODD NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PHOSPHORUS ISOTOPES; PHOSPHORUS-GROUP TRANSFERASES; PROTEINS; RADIOISOTOPES; RODENTS; TRANSFERASES; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats


                    Gandy, S, Czernik, A J, and Greengard, P. Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca sup 2+ /calmodulin-dependent protein kinase II.  United States: N. p., 1988. 
        Web.  doi:10.1073/pnas.85.16.6218.

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                    Gandy, S, Czernik, A J, & Greengard, P. Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca sup 2+ /calmodulin-dependent protein kinase II.  United States.  https://doi.org/10.1073/pnas.85.16.6218

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                    Gandy, S, Czernik, A J, and Greengard, P. 1988.  
        "Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca sup 2+ /calmodulin-dependent protein kinase II".  United States.  https://doi.org/10.1073/pnas.85.16.6218.

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@article{osti_5405760,

  title        = {Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca sup 2+ /calmodulin-dependent protein kinase II},

  author       = {Gandy, S and Czernik, A J and Greengard, P},

  abstractNote = {The amino acid sequence of the Alzheimer disease amyloid precursor (ADAP) has been deduced from the corresponding cDNA, and hydropathy analysis of the sequence suggest a receptor-like structure with a single transmembrane domain. The putative cytoplasmic domain of ADAP contains potential sites for serine and threonine phosphorylation. In the present study, synthetic peptides derived from this domain were used as model substrates for various purified protein kinases. Protein kinase C rapidly catalyzed the phosphorylation of a peptide corresponding to amino acid residues 645-661 of ADAP. Ca{sup 2+}/calmodulin-dependent protein kinase II phosphorylated ADAP peptide (645-661) on Thr-654 and Ser-655. Using rat cerebral cortex synaptosomes prelabeled with {sup 32}P{sub i}, a {sup 32}P-labeled phosphoprotein of {approx}135 kDa was immunoprecipitated by using antisera prepared against ADAP peptide(597-624), consistent with the possibility that the holoform of ADAP in rat brain is a phosphoprotein. Based on analogy with the effect of phosphorylation by protein kinase C of juxtamembrane residues in the cytoplasmic domain of the epidermal growth factor receptor and the interleukin 2 receptor, phosphorylation of ADAP may target it for internalization.},

  doi          = {10.1073/pnas.85.16.6218},

  url          = {https://www.osti.gov/biblio/5405760},
  journal      = {Proceedings of the National Academy of Sciences of the United States of America; (USA)},

  issn         = {0027-8424},

  number       = ,

  volume       = 85:16,

  place        = {United States},

  year         = {Mon Aug 01 00:00:00 EDT 1988},

  month        = {Mon Aug 01 00:00:00 EDT 1988}

}

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