Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1990 Jan; 87(2): 821–825.

Stimulation of casein kinase II by epidermal growth factor: relationship between the physiological activity of the kinase and the phosphorylation state of its beta subunit.


To determine relationships between the hormonal activation of casein kinase II and its phosphorylation state, epidermal growth factor (EGF)-treated and EGF-naive human A-431 carcinoma cells were cultured in the presence of [32P]orthophosphate. Immunoprecipitation experiments indicated that casein kinase II in the cytosol of EGF-treated cells contained approximately 3-fold more incorporated [32P]phosphate than did its counterpart in untreated cells. Levels of kinase phosphorylation paralleled levels of kinase activity over a wide range of EGF concentrations as well as over a time course of hormone action. Approximately 97% of the incorporated [32P]phosphate was found in the beta subunit of casein kinase II. Both activated and hormone-naive kinase contained radioactive phosphoserine and phosphothreonine but no phosphotyrosine. On the basis of proteolytic mapping experiments, EGF treatment of A-431 cells led to an increase in the average [32P]phosphate content (i.e., hyperphosphorylation) of casein kinase II beta subunit peptides which were modified prior to hormone treatment. Finally, the effect of alkaline phosphatase on the reaction kinetics of activated casein kinase II indicated that hormonal stimulation of the kinase resulted from the increase in its phosphorylation state.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hathaway GM, Traugh JA. Casein kinases--multipotential protein kinases. Curr Top Cell Regul. 1982;21:101–127. [PubMed]
  • Edelman AM, Blumenthal DK, Krebs EG. Protein serine/threonine kinases. Annu Rev Biochem. 1987;56:567–613. [PubMed]
  • Krebs EG, Eisenman RN, Kuenzel EA, Litchfield DW, Lozeman FJ, Lüscher B, Sommercorn J. Casein kinase II as a potentially important enzyme concerned with signal transduction. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 1):77–84. [PubMed]
  • Hathaway GM, Traugh JA. Cyclic nucleotide-independent protein kinases from rabbit reticulocytes. Purification of casein kinases. J Biol Chem. 1979 Feb 10;254(3):762–768. [PubMed]
  • Dahmus ME. Purification and properties of calf thymus casein kinases I and II. J Biol Chem. 1981 Apr 10;256(7):3319–3325. [PubMed]
  • Hathaway GM, Zoller MJ, Traugh JA. Identification of the catalytic subunit of casein kinase II by affinity labeling with 5'-p-fluorosulfonylbenzoyl adenosine. J Biol Chem. 1981 Nov 25;256(22):11442–11446. [PubMed]
  • Cochet C, Chambaz EM. Oligomeric structure and catalytic activity of G type casein kinase. Isolation of the two subunits and renaturation experiments. J Biol Chem. 1983 Feb 10;258(3):1403–1406. [PubMed]
  • Meggio F, Pinna LA. Subunit structure and autophosphorylation mechanism of casein kinase-TS (type-2) from rat liver cytosol. Eur J Biochem. 1984 Dec 17;145(3):593–599. [PubMed]
  • Saxena A, Padmanabha R, Glover CV. Isolation and sequencing of cDNA clones encoding alpha and beta subunits of Drosophila melanogaster casein kinase II. Mol Cell Biol. 1987 Oct;7(10):3409–3417. [PMC free article] [PubMed]
  • Takio K, Kuenzel EA, Walsh KA, Krebs EG. Amino acid sequence of the beta subunit of bovine lung casein kinase II. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4851–4855. [PMC free article] [PubMed]
  • Glover CV, Shelton ER, Brutlag DL. Purification and characterization of a type II casein kinase from Drosophila melanogaster. J Biol Chem. 1983 Mar 10;258(5):3258–3265. [PubMed]
  • Sommercorn J, Mulligan JA, Lozeman FJ, Krebs EG. Activation of casein kinase II in response to insulin and to epidermal growth factor. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8834–8838. [PMC free article] [PubMed]
  • Klarlund JK, Czech MP. Insulin-like growth factor I and insulin rapidly increase casein kinase II activity in BALB/c 3T3 fibroblasts. J Biol Chem. 1988 Nov 5;263(31):15872–15875. [PubMed]
  • Ackerman P, Osheroff N. Regulation of casein kinase II activity by epidermal growth factor in human A-431 carcinoma cells. J Biol Chem. 1989 Jul 15;264(20):11958–11965. [PubMed]
  • Carroll D, Marshak DR. Serum-stimulated cell growth causes oscillations in casein kinase II activity. J Biol Chem. 1989 May 5;264(13):7345–7348. [PubMed]
  • Savage CR, Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed]
  • Dahmus GK, Glover CV, Brutlag DL, Dahmus ME. Similarities in structure and function of calf thymus and Drosophila casein kinase II. J Biol Chem. 1984 Jul 25;259(14):9001–9006. [PubMed]
  • Kuenzel EA, Krebs EG. A synthetic peptide substrate specific for casein kinase II. Proc Natl Acad Sci U S A. 1985 Feb;82(3):737–741. [PMC free article] [PubMed]
  • Kuenzel EA, Mulligan JA, Sommercorn J, Krebs EG. Substrate specificity determinants for casein kinase II as deduced from studies with synthetic peptides. J Biol Chem. 1987 Jul 5;262(19):9136–9140. [PubMed]
  • Sommercorn J, Krebs EG. Induction of casein kinase II during differentiation of 3T3-L1 cells. J Biol Chem. 1987 Mar 15;262(8):3839–3843. [PubMed]
  • Ackerman P, Glover CV, Osheroff N. Phosphorylation of DNA topoisomerase II in vivo and in total homogenates of Drosophila Kc cells. The role of casein kinase II. J Biol Chem. 1988 Sep 5;263(25):12653–12660. [PubMed]
  • Soderquist AM, Carpenter G. Biosynthesis of the epidermal growth factor receptor in cultured cells. Methods Enzymol. 1987;146:49–63. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Hunter T, Sefton BM. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. [PMC free article] [PubMed]
  • Cleveland DW, Fischer SG, Kirschner MW, Laemmli UK. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed]
  • Stoscheck CM, Carpenter G. Biology of the A-431 cell: a useful organism for hormone research. J Cell Biochem. 1983;23(1-4):191–202. [PubMed]
  • Carpenter G, Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. [PubMed]
  • Meggio F, Brunati AM, Pinna LA. Autophosphorylation of type 2 casein kinase TS at both its alpha- and beta-subunits. Influence of different effectors. FEBS Lett. 1983 Aug 22;160(1-2):203–208. [PubMed]
  • Flockhart DA, Corbin JD. Regulatory mechanisms in the control of protein kinases. CRC Crit Rev Biochem. 1982 Feb;12(2):133–186. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Save items

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    Related information in MedGen
  • Protein
    Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...