Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation

被引:53
作者
Bruecher-Encke, B
Griffin, JD
Neel, BG
Lorenz, U
机构
[1] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA
[2] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Dept Canc Biol, Boston, MA 02215 USA
[3] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA USA
[5] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA
关键词
tyrosine phosphatase; differentiation; leukemia; erythroid lineage; myeloid lineage;
D O I
10.1038/sj.leu.2402214
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The erythro-megakaryoblastic leukemia cell line K562 undergoes erythroid or myeloid differentiation in response to treatment with various inducing agents. We observed that expression of the SH2-containing protein tyrosine phosphatase SHP-1 was induced upon exposure of K562 cells to differentiating agents. Under the same conditions, expression of SHP-2, a close relative of SHP-1, and the more distantly related PTP-1B remained unchanged. Induction of SHP-1 expression correlates with dephosphorylation of a specific and limited set of tyrosyl phosphoproteins, suggesting that dephosphorylation of these proteins may be important for the differentiation process. Importantly, expression of exogenous SHP-1 inhibits K562 proliferation and alters the adhesion properties of these cells, indicating a more differentiated phenotype. Moreover, SHP-1 is found in a complex with both p210 Bcr-Abl and p190 Bcr-Abl, suggesting that it may regulate Bcr-Abl or Bcr-Abl-associated phosphotyrosyl proteins. Our results indicate that induction of SHP-1 expression is important for K562 differentiation in response to various inducers and raise the possibility that functional inactivation of SHP-1 may play a role in progression to blast crisis in chronic myelogenous leukemia.
引用
收藏
页码:1424 / 1432
页数:9
相关论文
共 47 条
[1]   THE BCR-C-ABL TYROSINE KINASE-ACTIVITY IS EXTINGUISHED BY TPA IN K562 LEUKEMIA-CELLS [J].
ALITALO, R .
FEBS LETTERS, 1987, 222 (02) :293-298
[2]   THE CHRONIC MYELOGENOUS LEUKEMIA SPECIFIC P210-PROTEIN IS THE PRODUCT OF THE BCR/ABL HYBRID GENE [J].
BEN-NERIAH, Y ;
DALEY, GQ ;
MESMASSON, AM ;
WITTE, ON ;
BALTIMORE, D .
SCIENCE, 1986, 233 (4760) :212-214
[3]   A NOVEL ABL PROTEIN EXPRESSED IN PHILADELPHIA-CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA [J].
CHAN, LC ;
KARHI, KK ;
RAYTER, SI ;
HEISTERKAMP, N ;
ERIDANI, S ;
POWLES, R ;
LAWLER, SD ;
GROFFEN, J ;
FOULKES, JG ;
GREAVES, MF ;
WIEDEMANN, LM .
NATURE, 1987, 325 (6105) :635-637
[4]   Regulation of colony-stimulating factor 1 receptor signaling by the SH2 domain-containing tyrosine phosphatase SHPTP1 [J].
Chen, HE ;
Chang, S ;
Trub, T ;
Neel, BG .
MOLECULAR AND CELLULAR BIOLOGY, 1996, 16 (07) :3685-3697
[5]   ABR AND BCR ARE MULTIFUNCTIONAL REGULATORS OF THE RHO-GTP-BINDING PROTEIN FAMILY [J].
CHUANG, TH ;
XU, X ;
KAARTINEN, V ;
HEISTERKAMP, N ;
GROFFEN, J ;
BOKOCH, GM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (22) :10282-10286
[6]   GENOMIC SEQUENCING [J].
CHURCH, GM ;
GILBERT, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (07) :1991-1995
[7]  
CORTEZ D, 1995, MOL CELL BIOL, V15, P5531
[8]  
DALEY GQ, 1991, ADV CANCER RES, V57, P151
[9]   Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes [J].
Delibrias, CC ;
Floettmann, JE ;
Rowe, M ;
Fearon, DT .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (09) :1575-1583
[10]  
DRUKER B, 1992, BLOOD, V79, P2215