The human papillomavirus type 16 E5 protein modulates phospholipase C-γ-1 activity and phosphatidyl inositol turnover in mouse fibroblasts

被引:21
作者
Crusius, K [1 ]
Kaszkin, M [1 ]
Kinzel, V [1 ]
Alonso, A [1 ]
机构
[1] Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany
关键词
phospholipids; phospholipases; membranes; kinases;
D O I
10.1038/sj.onc.1203075
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The human papillomavirus type 16 E5 (HPV16-E5) protein is a membrane protein that has been associated with malignant growth. The protein affects growth factor-mediated signal transduction in a ligand-dependent manner. We show now that E5 expression in A31 fibroblasts results in an increased level of diacylglycerol (DAG) and inositol phosphates. Immunoprecipitation of phospholipase C-gamma-1 (PLC-gamma-1) with specific antibodies and immunoblotting with anti-phosphotyrosine antibodies reveal a large increase in tyrosine phosphorylation of the enzyme in ES-expressing cells compared to control vector-transfected cells. This activation of tyrosine phosphorylation is growth factor independent. In addition, an enhanced formation of phosphatidic acid (PA) was observed in E5 cells. This increase did not result from activation of phospholipase D (PLD), although the enzyme was activatable by treatment with phorbol ester. Thus, a phosphohydrolase-mediated DAG synthesis from PLD-produced PA can be excluded. The observed effects were not further enhanced by EGF showing that the presence of the growth factor is not necessary for maintaining permanent activation of PLC-gamma-1 in E5-expressing cells. The DAG- and inositol phosphate-mediated signal cascade within the cells is thus effectively uncoupled from external control via EGF and its receptor in the presence of E5 protein.
引用
收藏
页码:6714 / 6718
页数:5
相关论文
共 36 条
  • [31] Specific inhibition of phorbol ester-stimulated phospholipase D by Clostridium sordellii lethal toxin and Clostridium difficile toxin B-1470 in HEK-293 cells -: Restoration by Ral GTPases
    Schmidt, M
    Voss, M
    Thiel, M
    Bauer, B
    Grannass, A
    Tapp, E
    Cool, RH
    de Gunzburg, J
    von Eichel-Streiber, C
    Jakobs, KH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (13) : 7413 - 7422
  • [32] Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D
    Singer, WD
    Brown, HA
    Sternweis, PC
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1997, 66 : 475 - 509
  • [33] THE E5 ONCOPROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16 TRANSFORMS FIBROBLASTS AND EFFECTS THE DOWN-REGULATION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN KERATINOCYTES
    STRAIGHT, SW
    HINKLE, PM
    JEWERS, RJ
    MCCANCE, DJ
    [J]. JOURNAL OF VIROLOGY, 1993, 67 (08) : 4521 - 4532
  • [34] WAGNER H, 1962, J LIPID RES, V3, P177
  • [35] WAHL M, 1988, J BIOL CHEM, V263, P7581
  • [36] STIMULATION OF PHOSPHOLIPASE-D BY EPIDERMAL GROWTH-FACTOR REQUIRES PROTEIN-KINASE-C ACTIVATION IN SWISS 3T3 CELLS
    YEO, EJ
    EXTON, JH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (08) : 3980 - 3988