Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Nov 8;91(23):11075–11079. doi: 10.1073/pnas.91.23.11075

Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor.

M Chinkers 1
PMCID: PMC45169  PMID: 7972012

Abstract

Protein kinase-related domains of unknown function are present in the JAK family of protein tyrosine kinases and in receptor/guanylyl cyclases. I used the yeast two-hybrid system to screen for proteins interacting with the kinase-like domain of the atrial natriuretic peptide (ANP) receptor/guanylyl cyclase. A yeast strain was constructed expressing a fusion of this kinase-like domain to the lexA DNA-binding domain and containing a HIS3 gene under the control of lexA upstream activating sequences. These yeast cells were transformed with a plasmid library of mouse embryo cDNA fragments fused to the VP16 transcriptional activation domain. Cells containing VP16-fusion proteins interacting with the lexA-kinase-like domain fusion protein were selected by growth in the absence of histidine. A partial-length cDNA clone isolated by using this approach encoded a protein that interacted specifically with the ANP-receptor protein kinase-like domain both in yeast cells and in vitro. Tissue-specific expression of a 2.2-kb mRNA hybridizing to this cDNA paralleled the known pattern of ANP-receptor mRNA expression. A full-length cDNA clone isolated from a rat lung library was predicted to encode a 55-kDa protein containing at its amino terminus a targeting domain that binds to the ANP-receptor kinase-like domain and containing at its carboxyl terminus a putative protein-serine phosphatase domain. This protein is a possible candidate for the phosphatase involved in desensitizing the ANP receptor. Targeting of regulatory proteins may be an important function of protein kinase-like domains.

Full text

PDF
11075

Images in this article

11077Image
on p.11077
11077Image
on p.11077
11078Image
on p.11078

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams M. D., Dubnick M., Kerlavage A. R., Moreno R., Kelley J. M., Utterback T. R., Nagle J. W., Fields C., Venter J. C. Sequence identification of 2,375 human brain genes. Nature. 1992 Feb 13;355(6361):632–634. doi: 10.1038/355632a0. [DOI] [PubMed] [Google Scholar]
  2. Barker H. M., Jones T. A., da Cruz e Silva E. F., Spurr N. K., Sheer D., Cohen P. T. Localization of the gene encoding a type I protein phosphatase catalytic subunit to human chromosome band 11q13. Genomics. 1990 Jun;7(2):159–166. doi: 10.1016/0888-7543(90)90536-4. [DOI] [PubMed] [Google Scholar]
  3. Bartel P., Chien C. T., Sternglanz R., Fields S. Elimination of false positives that arise in using the two-hybrid system. Biotechniques. 1993 Jun;14(6):920–924. [PubMed] [Google Scholar]
  4. Baur A., Schaaff-Gerstenschläger I., Boles E., Miosga T., Rose M., Zimmermann F. K. Sequence of a 4.8 kb fragment of Saccharomyces cerevisiae chromosome II including three essential open reading frames. Yeast. 1993 Mar;9(3):289–293. doi: 10.1002/yea.320090308. [DOI] [PubMed] [Google Scholar]
  5. Brewis N. D., Cohen P. T. Protein phosphatase X has been highly conserved during mammalian evolution. Biochim Biophys Acta. 1992 Dec 29;1171(2):231–233. doi: 10.1016/0167-4781(92)90129-n. [DOI] [PubMed] [Google Scholar]
  6. Chinkers M., Garbers D. L., Chang M. S., Lowe D. G., Chin H. M., Goeddel D. V., Schulz S. A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor. Nature. 1989 Mar 2;338(6210):78–83. doi: 10.1038/338078a0. [DOI] [PubMed] [Google Scholar]
  7. Chinkers M., Garbers D. L. The protein kinase domain of the ANP receptor is required for signaling. Science. 1989 Sep 22;245(4924):1392–1394. doi: 10.1126/science.2571188. [DOI] [PubMed] [Google Scholar]
  8. Chinkers M., Wilson E. M. Ligand-independent oligomerization of natriuretic peptide receptors. Identification of heteromeric receptors and a dominant negative mutant. J Biol Chem. 1992 Sep 15;267(26):18589–18597. [PubMed] [Google Scholar]
  9. Cohen P. T. Important roles for novel protein phosphatases dephosphorylating serine and threonine residues. Biochem Soc Trans. 1993 Nov;21(4):884–888. doi: 10.1042/bst0210884. [DOI] [PubMed] [Google Scholar]
  10. Drewett J. G., Garbers D. L. The family of guanylyl cyclase receptors and their ligands. Endocr Rev. 1994 Apr;15(2):135–162. doi: 10.1210/edrv-15-2-135. [DOI] [PubMed] [Google Scholar]
  11. Fields S., Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. doi: 10.1038/340245a0. [DOI] [PubMed] [Google Scholar]
  12. Giri P. R., Higuchi S., Kincaid R. L. Chromosomal mapping of the human genes for the calmodulin-dependent protein phosphatase (calcineurin) catalytic subunit. Biochem Biophys Res Commun. 1991 Nov 27;181(1):252–258. doi: 10.1016/s0006-291x(05)81410-x. [DOI] [PubMed] [Google Scholar]
  13. Harpur A. G., Andres A. C., Ziemiecki A., Aston R. R., Wilks A. F. JAK2, a third member of the JAK family of protein tyrosine kinases. Oncogene. 1992 Jul;7(7):1347–1353. [PubMed] [Google Scholar]
  14. Honoré B., Leffers H., Madsen P., Rasmussen H. H., Vandekerckhove J., Celis J. E. Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1. J Biol Chem. 1992 Apr 25;267(12):8485–8491. [PubMed] [Google Scholar]
  15. Joshi M., Dwyer D. M., Nakhasi H. L. Cloning and characterization of differentially expressed genes from in vitro-grown 'amastigotes' of Leishmania donovani. Mol Biochem Parasitol. 1993 Apr;58(2):345–354. doi: 10.1016/0166-6851(93)90057-5. [DOI] [PubMed] [Google Scholar]
  16. Kieffer L. J., Seng T. W., Li W., Osterman D. G., Handschumacher R. E., Bayney R. M. Cyclophilin-40, a protein with homology to the P59 component of the steroid receptor complex. Cloning of the cDNA and further characterization. J Biol Chem. 1993 Jun 15;268(17):12303–12310. [PubMed] [Google Scholar]
  17. Koller K. J., de Sauvage F. J., Lowe D. G., Goeddel D. V. Conservation of the kinaselike regulatory domain is essential for activation of the natriuretic peptide receptor guanylyl cyclases. Mol Cell Biol. 1992 Jun;12(6):2581–2590. doi: 10.1128/mcb.12.6.2581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kunz J., Hall M. N. Cyclosporin A, FK506 and rapamycin: more than just immunosuppression. Trends Biochem Sci. 1993 Sep;18(9):334–338. doi: 10.1016/0968-0004(93)90069-y. [DOI] [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Nicolet C. M., Craig E. A. Isolation and characterization of STI1, a stress-inducible gene from Saccharomyces cerevisiae. Mol Cell Biol. 1989 Sep;9(9):3638–3646. doi: 10.1128/mcb.9.9.3638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Peattie D. A., Harding M. W., Fleming M. A., DeCenzo M. T., Lippke J. A., Livingston D. J., Benasutti M. Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10974–10978. doi: 10.1073/pnas.89.22.10974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Potter L. R., Garbers D. L. Protein kinase C-dependent desensitization of the atrial natriuretic peptide receptor is mediated by dephosphorylation. J Biol Chem. 1994 May 20;269(20):14636–14642. [PubMed] [Google Scholar]
  24. Schulz S., Singh S., Bellet R. A., Singh G., Tubb D. J., Chin H., Garbers D. L. The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family. Cell. 1989 Sep 22;58(6):1155–1162. doi: 10.1016/0092-8674(89)90513-8. [DOI] [PubMed] [Google Scholar]
  25. Vojtek A. B., Hollenberg S. M., Cooper J. A. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell. 1993 Jul 16;74(1):205–214. doi: 10.1016/0092-8674(93)90307-c. [DOI] [PubMed] [Google Scholar]
  26. Ward A. C. Single-step purification of shuttle vectors from yeast for high frequency back-transformation into E. coli. Nucleic Acids Res. 1990 Sep 11;18(17):5319–5319. doi: 10.1093/nar/18.17.5319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilcox J. N., Augustine A., Goeddel D. V., Lowe D. G. Differential regional expression of three natriuretic peptide receptor genes within primate tissues. Mol Cell Biol. 1991 Jul;11(7):3454–3462. doi: 10.1128/mcb.11.7.3454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wilks A. F., Harpur A. G., Kurban R. R., Ralph S. J., Zürcher G., Ziemiecki A. Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. Mol Cell Biol. 1991 Apr;11(4):2057–2065. doi: 10.1128/mcb.11.4.2057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. da Cruz e Silva O. B., Cohen P. T. A second catalytic subunit of type-2A protein phosphatase from rabbit skeletal muscle. FEBS Lett. 1987 Dec 21;226(1):176–178. doi: 10.1016/0014-5793(87)80574-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES