Molecular Biology Reports

, Volume 34, Issue 3, pp 137–144 | Cite as

Cloning and characterization of the human gene RAP2C, a novel member of Ras family, which activates transcriptional activities of SRE

  • Zekun Guo
  • Jian Yuan
  • Wenwen Tang
  • Xinya Chen
  • Xiuting Gu
  • Kuntian Luo
  • Yingli Wang
  • Bo Wan
  • Long Yu
Original Paper


The Ras family regulates a wide variety of cellular functions that include cell growth, differentiation, and apoptosis. In this study, we identified a novel human gene named RAP2C, isolated from human testis cDNA library, and mapped to Xq26.2 by searching the UCSC genomic database. The RAP2C cDNA contains an open reading frame of 552 bp, encoding a putative protein of 183 amino acid residues. The predicted protein contains a RAS domain. By RT-PCR analysis in various tissues, RAP2C was found to be principally expressed in the liver, skeletal muscle, prostate, uterus, rectum, stomach, and bladder and to a less extent in brain, kidney, pancreas, and bone marrow. RAP2C protein was located in cytoplasm when overexpressed in COS-7 cells. Reporter gene assays showed that overexpression of RAP2C in HEK293T cells activated the transcriptional activities of serum response element (SRE). These results indicate that RAP2C is a novel member of the Ras family, belonging to the Rap branch of small GTPase proteins and may be involved in SRE-mediated gene transcription.


RAP2C SRE Transcription 



This work was supported by the National 973 Program, 863 High Technology Program, and the National Natural Science Foundation of China. Database accession no.: NM_021183 (GenBank).


  1. 1.
    Campbell SL, Khosravi-Far R, Rossman KL, Clark GJ, Der CJ (1998) Increasing complexity of Ras signaling. Oncogene 17:1395–1413PubMedCrossRefGoogle Scholar
  2. 2.
    Kaibuchi K, Kuroda S, Amano M (1999) Regulation of cytoskeletons and cell adhesions by the Rho-family GTPases. Annu Rev Biochem 68:459–486PubMedCrossRefGoogle Scholar
  3. 3.
    Yuan J, Shan Y, Chen X, Tang W, Luo K, Ni J, Wan B, Yu L (2005) Identification and characterization of RHEBL1, a novel member of Ras family, which activates transcriptional activities of NF-κB. Mol Biol Rep 32:205–214PubMedCrossRefGoogle Scholar
  4. 4.
    Pizon V, Lerosey I, Chardin P, Tavitian A (1988) Nucleotide sequence of a human cDNA encoding a ras-related protein (rap1B). Nucleic Acids Res 16:7719PubMedCrossRefGoogle Scholar
  5. 5.
    Pizon V, Chardin P, Lerosey I, Olofsson B, Tavitian A (1988) Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the ‘effector’ region. Oncogene 3:201–204PubMedGoogle Scholar
  6. 6.
    Ohmstede CA, Farrel FX, Reep BR, Clemetson KJ. Lapetina EG (1990) RAP2B: a RAS-related GTP-binding protein from platelets. Proc Natl Acad Sci USA 87:6527–6531PubMedCrossRefGoogle Scholar
  7. 7.
    Rodriguez-Viviana P, Warne P, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J (1994) Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature 370:527–532CrossRefGoogle Scholar
  8. 8.
    Wolthuis RMF, Bauer B, van’t Veer LJ, de Vries-Smits AMM, Cool R, Spaargaren M, Wittinghofer A, Burgering BMT, Bos JL (1996) RalGDS-like factor (Rlf) is a novel Ras and Rap 1A-associating protein. Oncogene 13:353–362PubMedGoogle Scholar
  9. 9.
    Herrmann C, Horn G, Spaargaren M, Wittinghofer A (1996) Differential interaction of the ras family GTP-binding proteins H-Ras, Rap1A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. J Biol Chem 271:6794–6800PubMedCrossRefGoogle Scholar
  10. 10.
    Nancy V, Wolthuis RM, de Tand MF, Janoueix-Lerosey I, Bos JL, de Gunzburg J (1999) Identification and Characterization of Potential Effector Molecules of the Ras-related GTPase Rap2. J Biol Chem 274(13):8737–8745PubMedCrossRefGoogle Scholar
  11. 11.
    Davis RJ (1993) The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268:14553–14556PubMedGoogle Scholar
  12. 12.
    Kyriakis JM, Banerjee P, Nikolakaki E, Dai T, Rubie EA, Ahmad MF, Avruch J, Woodgett JR (1994) The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369:156–160PubMedCrossRefGoogle Scholar
  13. 13.
    Han J, Lee JD, Ribbs L, Ulevitch RJ (1994) A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265:808–811PubMedCrossRefGoogle Scholar
  14. 14.
    Pearson EJ, Wilsbacher G, Swantek J, Karandikar J, Xu M, Cobb MH (1999) New insights into the control of MAP kinase pathways. Exp Cell Res 253:255–270PubMedCrossRefGoogle Scholar
  15. 15.
    Tang WW, Yuan J, Chen XY, Shan YX, Luo KT, Guo ZK, Zhang Y, Wan B, Yu L (2005) Cloning and characterization of the CDZFP gene which encodes a putative zinc finger protein. DNA Seq 16:391–196PubMedCrossRefGoogle Scholar
  16. 16.
    Wickens M (1990) How the messenger got its tail: Addition of poly(A) in the nucleus. Trends Biochem Sci 15:277–281PubMedCrossRefGoogle Scholar
  17. 17.
    Lowy DR, Willumsen BM (1993) Function and regulation of Ras. Annu Rev Biochem 62:851–891PubMedCrossRefGoogle Scholar
  18. 18.
    Fu HW, Casey PJ (1999) Enzymology and biology of CaaX protein prenylation. Recent Prog Horm Res 54:315–42PubMedGoogle Scholar
  19. 19.
    Moores SL, Scholber MD, Mosser SD, Rands E, O’Hara MB, Garsky VM, Marshall MS, Pompliano DL, Gibbs JM (1991) J Biol Chem 266:14603–14610PubMedGoogle Scholar
  20. 20.
    Cox AD, Der CJ (1992) The ras/cholesterol connection: implications for ras oncogenicity. Crit Rev Oncog 3:365–400PubMedGoogle Scholar
  21. 21.
    Farrell F, Torti M, Lapetina EG (1992) Rap proteins: investigating their role in cell function. J Lab Clin Med 120:533–537PubMedGoogle Scholar
  22. 22.
    Kawata M, Farnsworth CC, Yoshida Y, Gelb MH, Glomset JA, Takai Y (1990) Posttranslationally processed structure of the human platelet protein smg p21B: evidence for geranylgeranylation and carboxyl methylation of the C-terminal cysteine. Proc Natl Acad Sci USA 87:8960–8964PubMedCrossRefGoogle Scholar
  23. 23.
    Winegar DA, Molina Y, Vedia L, Lapetina EG (1991) Isoprenylation of rap2 proteins in platelets and human erythroleukemia cells. J Biol Chem 266:4381–4386PubMedGoogle Scholar
  24. 24.
    Herrera RE, Shaw PE, Nordheim A (1989) Occupation of the c-fos serum response element in vivo by a multi-protein complex is unaltered by growth factor induction. Nature 340:68–70PubMedCrossRefGoogle Scholar
  25. 25.
    Li SJ, Wang DZ, Wang ZG, Richardson JA, Olson EN (2003) The serum response factor coactivator myocardin is required for vascular smooth muscle development. Proc Natl Acad Sci USA 100(16):9366–9370PubMedCrossRefGoogle Scholar
  26. 26.
    Christian SL, Lee RL, McLeod SJ, Burgess AE, Li AH, Dang-Lawson M, Lin KB, Gold MR (2003) Activation of the Rap GTPases in B lymphocytes modulates B Cell antigen receptor-induced activation of Akt but has no effect on MAPK activation. J Biol Chem 278:41756–41767PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • Zekun Guo
    • 1
    • 2
  • Jian Yuan
    • 1
  • Wenwen Tang
    • 1
  • Xinya Chen
    • 1
  • Xiuting Gu
    • 1
  • Kuntian Luo
    • 1
  • Yingli Wang
    • 1
  • Bo Wan
    • 1
  • Long Yu
    • 1
  1. 1.State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science Fudan University ShanghaiPeople’s Republic of China
  2. 2.School of Life Science Northwest Sci-Tech University of Agriculture and ForestryYanglingPeople’s Republic of China

Personalised recommendations