Abstract
The protein-tyrosine phosphatase epsilon (PTP epsilon) is a transmembranal, receptor-type protein that possesses two phosphatase catalytic domains characteristic of transmembranal phosphatases. Here we demonstrate the existence of a nontransmembranal isoform of PTP epsilon, PTP epsilon-cytoplasmic. PTP epsilon-cytoplasmic and the transmembranal isoform of PTP epsilon have separate, nonoverlapping expression patterns. Further, the data clearly indicate that control of which of the two isoforms is to be expressed is initiated at the transcriptional level, suggesting that they have distinct physiological roles. PTP epsilon-cytoplasmic mRNA is the product of a delayed early response gene in NIH 3T3 fibroblasts, and its transcription is regulated through a pathway that requires protein kinase C. The human homologue of PTP epsilon-cytoplasmic has also been cloned and is strongly up-regulated in the early stages of phorbol 12-tetradecanoate 13-acetate-induced differentiation of HL-60 cells. Sequence analysis indicates and cellular fractionation experiments confirm that this isoform is a cytoplasmic molecule. PTP epsilon-cytoplasmic is therefore the initial example to our knowledge of a nontransmembranal protein-tyrosine phosphatase that contains two tandem of catalytic domains.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Birnie G. D. The HL60 cell line: a model system for studying human myeloid cell differentiation. Br J Cancer Suppl. 1988 Dec;9:41–45. [PMC free article] [PubMed] [Google Scholar]
- Champion-Arnaud P., Gesnel M. C., Foulkes N., Ronsin C., Sassone-Corsi P., Breathnach R. Activation of transcription via AP-1 or CREB regulatory sites is blocked by protein tyrosine phosphatases. Oncogene. 1991 Jul;6(7):1203–1209. [PubMed] [Google Scholar]
- Charbonneau H., Tonks N. K. 1002 protein phosphatases? Annu Rev Cell Biol. 1992;8:463–493. doi: 10.1146/annurev.cb.08.110192.002335. [DOI] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Daum G., Regenass S., Sap J., Schlessinger J., Fischer E. H. Multiple forms of the human tyrosine phosphatase RPTP alpha. Isozymes and differences in glycosylation. J Biol Chem. 1994 Apr 8;269(14):10524–10528. [PubMed] [Google Scholar]
- Edwards J. B., Delort J., Mallet J. Oligodeoxyribonucleotide ligation to single-stranded cDNAs: a new tool for cloning 5' ends of mRNAs and for constructing cDNA libraries by in vitro amplification. Nucleic Acids Res. 1991 Oct 11;19(19):5227–5232. doi: 10.1093/nar/19.19.5227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farago A., Nishizuka Y. Protein kinase C in transmembrane signalling. FEBS Lett. 1990 Aug 1;268(2):350–354. doi: 10.1016/0014-5793(90)81284-u. [DOI] [PubMed] [Google Scholar]
- Fischer E. H., Charbonneau H., Tonks N. K. Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes. Science. 1991 Jul 26;253(5018):401–406. doi: 10.1126/science.1650499. [DOI] [PubMed] [Google Scholar]
- Halazonetis T. D., Georgopoulos K., Greenberg M. E., Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell. 1988 Dec 2;55(5):917–924. doi: 10.1016/0092-8674(88)90147-x. [DOI] [PubMed] [Google Scholar]
- Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 1995 Jan 27;80(2):225–236. doi: 10.1016/0092-8674(95)90405-0. [DOI] [PubMed] [Google Scholar]
- Krueger N. X., Streuli M., Saito H. Structural diversity and evolution of human receptor-like protein tyrosine phosphatases. EMBO J. 1990 Oct;9(10):3241–3252. doi: 10.1002/j.1460-2075.1990.tb07523.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanahan A., Williams J. B., Sanders L. K., Nathans D. Growth factor-induced delayed early response genes. Mol Cell Biol. 1992 Sep;12(9):3919–3929. doi: 10.1128/mcb.12.9.3919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larsson L. G., Pettersson M., Oberg F., Nilsson K., Lüscher B. Expression of mad, mxi1, max and c-myc during induced differentiation of hematopoietic cells: opposite regulation of mad and c-myc. Oncogene. 1994 Apr;9(4):1247–1252. [PubMed] [Google Scholar]
- Leder A., Kuo A., Cardiff R. D., Sinn E., Leder P. v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9178–9182. doi: 10.1073/pnas.87.23.9178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maeda K., Imae Y. Thermosensory transduction in Escherichia coli: inhibition of the thermoresponse by L-serine. Proc Natl Acad Sci U S A. 1979 Jan;76(1):91–95. doi: 10.1073/pnas.76.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matthews R. J., Cahir E. D., Thomas M. L. Identification of an additional member of the protein-tyrosine-phosphatase family: evidence for alternative splicing in the tyrosine phosphatase domain. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4444–4448. doi: 10.1073/pnas.87.12.4444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McLaughlin S., Dixon J. E. Alternative splicing gives rise to a nuclear protein tyrosine phosphatase in Drosophila. J Biol Chem. 1993 Apr 5;268(10):6839–6842. [PubMed] [Google Scholar]
- Mei L., Doherty C. A., Huganir R. L. RNA splicing regulates the activity of a SH2 domain-containing protein tyrosine phosphatase. J Biol Chem. 1994 Apr 22;269(16):12254–12262. [PubMed] [Google Scholar]
- Mosinger B., Jr, Tillmann U., Westphal H., Tremblay M. L. Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):499–503. doi: 10.1073/pnas.89.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muller W. J., Sinn E., Pattengale P. K., Wallace R., Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell. 1988 Jul 1;54(1):105–115. doi: 10.1016/0092-8674(88)90184-5. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. The Albert Lasker Medical Awards. The family of protein kinase C for signal transduction. JAMA. 1989 Oct 6;262(13):1826–1833. [PubMed] [Google Scholar]
- Noguchi T., Metz R., Chen L., Mattéi M. G., Carrasco D., Bravo R. Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth. Mol Cell Biol. 1993 Sep;13(9):5195–5205. doi: 10.1128/mcb.13.9.5195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oon S. H., Hong A., Yang X., Chia W. Alternative splicing in a novel tyrosine phosphatase gene (DPTP4E) of Drosophila melanogaster generates two large receptor-like proteins which differ in their carboxyl termini. J Biol Chem. 1993 Nov 15;268(32):23964–23971. [PubMed] [Google Scholar]
- Pan M. G., Rim C., Lu K. P., Florio T., Stork P. J. Cloning and expression of two structurally distinct receptor-linked protein-tyrosine phosphatases generated by RNA processing from a single gene. J Biol Chem. 1993 Sep 15;268(26):19284–19291. [PubMed] [Google Scholar]
- Pei D., Lorenz U., Klingmüller U., Neel B. G., Walsh C. T. Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains. Biochemistry. 1994 Dec 27;33(51):15483–15493. doi: 10.1021/bi00255a030. [DOI] [PubMed] [Google Scholar]
- Pot D. A., Dixon J. E. A thousand and two protein tyrosine phosphatases. Biochim Biophys Acta. 1992 Jul 22;1136(1):35–43. doi: 10.1016/0167-4889(92)90082-m. [DOI] [PubMed] [Google Scholar]
- Rich B. E., Steitz J. A. Human acidic ribosomal phosphoproteins P0, P1, and P2: analysis of cDNA clones, in vitro synthesis, and assembly. Mol Cell Biol. 1987 Nov;7(11):4065–4074. doi: 10.1128/mcb.7.11.4065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sachs A. B. Messenger RNA degradation in eukaryotes. Cell. 1993 Aug 13;74(3):413–421. doi: 10.1016/0092-8674(93)80043-e. [DOI] [PubMed] [Google Scholar]
- Shifrin V. I., Neel B. G. Growth factor-inducible alternative splicing of nontransmembrane phosphotyrosine phosphatase PTP-1B pre-mRNA. J Biol Chem. 1993 Dec 5;268(34):25376–25384. [PubMed] [Google Scholar]
- Stewart T. A., Pattengale P. K., Leder P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell. 1984 Oct;38(3):627–637. doi: 10.1016/0092-8674(84)90257-5. [DOI] [PubMed] [Google Scholar]
- Sun H., Charles C. H., Lau L. F., Tonks N. K. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell. 1993 Nov 5;75(3):487–493. doi: 10.1016/0092-8674(93)90383-2. [DOI] [PubMed] [Google Scholar]
- Sun H., Tonks N. K. The coordinated action of protein tyrosine phosphatases and kinases in cell signaling. Trends Biochem Sci. 1994 Nov;19(11):480–485. doi: 10.1016/0968-0004(94)90134-1. [DOI] [PubMed] [Google Scholar]
- Townley R., Shen S. H., Banville D., Ramachandran C. Inhibition of the activity of protein tyrosine phosphate 1C by its SH2 domains. Biochemistry. 1993 Dec 14;32(49):13414–13418. doi: 10.1021/bi00212a006. [DOI] [PubMed] [Google Scholar]
- Trowbridge I. S., Thomas M. L. CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Annu Rev Immunol. 1994;12:85–116. doi: 10.1146/annurev.iy.12.040194.000505. [DOI] [PubMed] [Google Scholar]
- Witters L. A., Blackshear P. J. Protein kinase C-mediated phosphorylation in intact cells. Methods Enzymol. 1987;141:412–424. doi: 10.1016/0076-6879(87)41087-2. [DOI] [PubMed] [Google Scholar]
- Zander N. F., Cool D. E., Diltz C. D., Rohrschneider L. R., Krebs E. G., Fischer E. H. Suppression of v-fms-induced transformation by overexpression of a truncated T-cell protein tyrosine phosphatase. Oncogene. 1993 May;8(5):1175–1182. [PubMed] [Google Scholar]