期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 90, 期 5, 页码 1026-1037出版社
WILEY
DOI: 10.1002/jcb.10727
关键词
protein tyrosine phosphatase; ITIM; SH2 domain; leukemia; lymphoma
资金
- NCI NIH HHS [CA75218] Funding Source: Medline
- NHLBI NIH HHS [HL57393] Funding Source: Medline
- PHS HHS [AL45858] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA075218] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL057393] Funding Source: NIH RePORTER
SHP-1 has been proposed to be a tumor suppressor gene for several cancers. The expression of SHP-1 protein is diminished or abolished in most leukemia and lymphoma cell lines and tissues, and in some non-hematopoietic cancer cell lines, such as estrogen receptor (ER) negative breast cancer cell lines and some colorectal cancer cell lines. However, we do not know whether the reduced SHP-1 expression is the cause of cancer diseases or the secondary effect of cancer developments. Here, we first demonstrate that SHP-1 has general tumor suppressing function in SHP-1 transfected cell lines. Transfected SHP-1 inhibits the growth of three lymphoma/leukemia cell lines (Ramos, H9, Jurkat) and one breast cancer cell line (HTB26). We also demonstrate a possible molecular mechanism for the tumor suppressing function of SHP-1: SHP-1 inhibits cell growth partly by negative regulation of activated JAK kinase. In addition, we find, for the first time, that SHP-1 down-regulates the level of TYK2 kinase in H9 cells and of JAK1 kinase in HTB26 cells, by accelerating their degradation. The SHP-1 accelerated degradation of JAK1 kinase in HTB26 cells was blocked with the treatment of MG132, a specific inhibitor for proteasome-mediated proteolysis. Our data suggest a new function of SHP-1 in the regulation of proteasome-mediated degradation pathway. (C) 2003Wiley-Liss,lnc.
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