Signal transduction by the CEACAM1 tumor suppressor - Phosphorylation of serine 503 is required for growth-inhibitory activity

被引:28
作者
Estrera, VT
Chen, DT
Luo, WP
Hixson, DC
Lin, SH
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA
[2] Univ Texas, Houston Hlth Sci Ctr, Dept Pediat, Houston, TX 77030 USA
[3] Univ Texas, Houston Hlth Sci Ctr, Ctr Acad & Reading Skills, Houston, TX 77030 USA
[4] Brown Univ, Rhode Isl Hosp, Dept Med Oncol, Providence, RI 02906 USA
关键词
D O I
10.1074/jbc.M008156200
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
CEACAM1 is a cell-cell adhesion molecule that mediates hemophilic cell adhesion. In addition, CEACAM1 was also shown to suppress the growth of prostate, breast, and colon tumors. Structural and functional analyses showed that the adhesion activity of CEACAM1 is mediated by its extracellular domain while its cytoplasmic domain is necessary and sufficient for growth-inhibitory activity. The signal pathways leading to CEACAM1-mediated growth suppression are not known. We studied the importance of phosphorylation of serine 503 in this growth-inhibitory signaling pathway. Full-length CEACAM1 was found to be phosphorylated in vivo in both tyrosine and serine residues. Mutation of tyrosine 488 to phenylalanine did not abolish the tumor-suppressive activity of CEACAM1, suggesting that phosphorylation at tyrosine 488 is not critical for CEACAM1's tumor-suppressive activity. Although expression of CEACAM1's cytoplasmic domain inhibited the growth of DU145 prostate cancer cells in vivo, mutation of serine 503 to alanine abolished the growth-inhibitory activity. Tn addition, the change of serine 503 to aspartic acid produced tumor-suppressive activity similar to that of the wild-type CEACAM1, These results suggested that phosphorylation at serine 503 is essential for CEACAM1's growth inhibitory function in vivo.
引用
收藏
页码:15547 / 15553
页数:7
相关论文
共 46 条
  • [1] Bamberger AM, 1998, AM J PATHOL, V152, P1401
  • [2] Cell biology - New clues to how proteins link up to run the cell
    Barinaga, M
    [J]. SCIENCE, 1999, 283 (5406) : 1247 - +
  • [3] Association of biliary glycoprotein with protein tyrosine phosphatase SHP-1 in malignant colon epithelial cells
    Beauchemin, N
    Kunath, T
    Robitaille, J
    Chow, B
    Turbide, C
    Daniels, E
    Veillette, A
    [J]. ONCOGENE, 1997, 14 (07) : 783 - 790
  • [4] BRUMMER J, 1995, ONCOGENE, V11, P1649
  • [5] PHOSPHORYLATION OF THE POLYMERIC IMMUNOGLOBULIN RECEPTOR REQUIRED FOR ITS EFFICIENT TRANSCYTOSIS
    CASANOVA, JE
    BREITFELD, PP
    ROSS, SA
    MOSTOV, KE
    [J]. SCIENCE, 1990, 248 (4956) : 742 - 745
  • [6] CHEUNG PH, 1993, J BIOL CHEM, V268, P24303
  • [7] THE CYTOPLASMIC DOMAIN OF C-CAM IS REQUIRED FOR C-CAM-MEDIATED ADHESION FUNCTION - STUDIES OF A C-CAM TRANSCRIPT CONTAINING AN UNSPLICED INTRON
    CHEUNG, PH
    CULIC, O
    QIU, YH
    EARLEY, K
    THOMPSON, N
    HIXSON, DC
    LIN, SH
    [J]. BIOCHEMICAL JOURNAL, 1993, 295 : 427 - 435
  • [8] DICTYOSTELIUM MYOSIN HEAVY-CHAIN PHOSPHORYLATION SITES REGULATE MYOSIN FILAMENT ASSEMBLY AND LOCALIZATION IN-VIVO
    EGELHOFF, TT
    LEE, RJ
    SPUDICH, JA
    [J]. CELL, 1993, 75 (02) : 363 - 371
  • [9] The cytoplasmic domain of C-CAM1 tumor suppressor is necessary and sufficient for suppressing the tumorigenicity of prostate cancer cells
    Estrera, VT
    Luo, WP
    Phan, D
    Earley, K
    Hixson, DC
    Lin, SH
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 263 (03) : 797 - 803
  • [10] 14-3-3-PROTEIN HOMOLOGS REQUIRED FOR THE DNA-DAMAGE CHECKPOINT IN FISSION YEAST
    FORD, JC
    ALKHODAIRY, F
    FOTOU, E
    SHELDRICK, KS
    GRIFFITHS, DJF
    CARR, AM
    [J]. SCIENCE, 1994, 265 (5171) : 533 - 535