東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Characterization of the transformati...

Harvard University.

FindBook

Google Book

Amazon

博客來

Characterization of the transformation and signal transduction properties of TEL/JAK2 fusion proteins associated with human leukemias.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Characterization of the transformation and signal transduction properties of TEL/JAK2 fusion proteins associated with human leukemias./
作者:	Frantsve, Julie Carolyn.
面頁冊數:	264 p.
附註:	Adviser: D. Gary Gilliland.
Contained By:	Dissertation Abstracts International63-01B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3038468
ISBN:	0493516263

Characterization of the transformation and signal transduction properties of TEL/JAK2 fusion proteins associated with human leukemias.
Frantsve, Julie Carolyn.

Characterization of the transformation and signal transduction properties of TEL/JAK2 fusion proteins associated with human leukemias. - 264 p.

Adviser: D. Gary Gilliland.

Thesis (Ph.D.)--Harvard University, 2002.

Three TEL/JAK2 fusion variants that are the consequence of t(9;12)(p24;p13) chromosomal translocations have been identified in patients with T-cell acute lymphoblastic leukemia, preB-cell acute lymphoblastic leukemia, and atypical chronic myelogenous leukemia. The translocations result in the fusion of the pointed domain (PNT) of TEL, which mediates oligomerization of the protein, to the JH1 kinase domain of JAK2. All fusion variants transform the murine hematopoietic cell line, Ba/F3, to factor independent growth and cause a myelo- and lymphoproliferative disease in a murine bone marrow transplant model. Mutational analysis has demonstrated that transformation of hematopoietic cells by TEL/JAK2 <italic>in vitro</italic> and <italic>in vivo</italic> requires the PNT domain of TEL as well as the kinase activity of the JAK2 JH1 domain. TEL/JAK2 activates STAT5, members of the RAS/MAP kinase pathway, members of the PI3K/AKT pathway, and engages the Gab2 adaptor protein. TEL/JAK2 murine bone marrow transplants conducted in a Stat5a/b deficient background indicate that Stat5 is essential for the TEL/JAK2-mediated disease, and transplants conducted in a Gab2 deficient background indicate that loss of this adaptor protein attenuates the myeloproliferative phenotype induced by TEL/JAK2. Expression of Socs-1, a member of the SOCS family of endogenous inhibitors of JAKs and STATs, inhibits engagement of each of these signaling pathways through two distinct mechanisms: inhibition of TEL/JAK2 kinase activity and proteasomal-mediated degradation of the fusion protein. Furthermore, Socs1 expression specifically inhibits <italic>in vitro</italic> and <italic>in vivo</italic> transformation by TEL/JAK2. Tyrosine phosphorylation of Socs1 by TEL/JAK2 regulates its ability to impair TEL/JAK2 transformation. These data demonstrate that TEL/JAK2 transforms hematopoietic cell lines and primary hematopoietic progenitor cells through activation of STAT5, the RAS/MAP kinase pathway and the PI3K/AKT pathway, and that expression of Socs1 can inhibit transformation. This research has further elucidated our understanding of the mechanism by which constitutively activated tyrosine kinases transform cells in human cancers.

ISBN: 0493516263Subjects--Topical Terms:

1017730
Biology, Genetics.

Characterization of the transformation and signal transduction properties of TEL/JAK2 fusion proteins associated with human leukemias.
LDR:03188nam 2200289 a 45 001 927668
005 20110425
008 110425s2002 eng d
020 $a 0493516263
035 $a (UnM)AAI3038468
035 $a AAI3038468
040 $a UnM $c UnM
100 1 $a Frantsve, Julie Carolyn. $3 1251232
245 1 0 $a Characterization of the transformation and signal transduction properties of TEL/JAK2 fusion proteins associated with human leukemias.
300 $a 264 p.
500 $a Adviser: D. Gary Gilliland.
500 $a Source: Dissertation Abstracts International, Volume: 63-01, Section: B, page: 0191.
502 $a Thesis (Ph.D.)--Harvard University, 2002.
520 $a Three TEL/JAK2 fusion variants that are the consequence of t(9;12)(p24;p13) chromosomal translocations have been identified in patients with T-cell acute lymphoblastic leukemia, preB-cell acute lymphoblastic leukemia, and atypical chronic myelogenous leukemia. The translocations result in the fusion of the pointed domain (PNT) of TEL, which mediates oligomerization of the protein, to the JH1 kinase domain of JAK2. All fusion variants transform the murine hematopoietic cell line, Ba/F3, to factor independent growth and cause a myelo- and lymphoproliferative disease in a murine bone marrow transplant model. Mutational analysis has demonstrated that transformation of hematopoietic cells by TEL/JAK2 <italic>in vitro</italic> and <italic>in vivo</italic> requires the PNT domain of TEL as well as the kinase activity of the JAK2 JH1 domain. TEL/JAK2 activates STAT5, members of the RAS/MAP kinase pathway, members of the PI3K/AKT pathway, and engages the Gab2 adaptor protein. TEL/JAK2 murine bone marrow transplants conducted in a Stat5a/b deficient background indicate that Stat5 is essential for the TEL/JAK2-mediated disease, and transplants conducted in a Gab2 deficient background indicate that loss of this adaptor protein attenuates the myeloproliferative phenotype induced by TEL/JAK2. Expression of Socs-1, a member of the SOCS family of endogenous inhibitors of JAKs and STATs, inhibits engagement of each of these signaling pathways through two distinct mechanisms: inhibition of TEL/JAK2 kinase activity and proteasomal-mediated degradation of the fusion protein. Furthermore, Socs1 expression specifically inhibits <italic>in vitro</italic> and <italic>in vivo</italic> transformation by TEL/JAK2. Tyrosine phosphorylation of Socs1 by TEL/JAK2 regulates its ability to impair TEL/JAK2 transformation. These data demonstrate that TEL/JAK2 transforms hematopoietic cell lines and primary hematopoietic progenitor cells through activation of STAT5, the RAS/MAP kinase pathway and the PI3K/AKT pathway, and that expression of Socs1 can inhibit transformation. This research has further elucidated our understanding of the mechanism by which constitutively activated tyrosine kinases transform cells in human cancers.
590 $a School code: 0084.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0307
690 $a 0369
690 $a 0992
710 2 0 $a Harvard University. $3 528741
773 0 $t Dissertation Abstracts International $g 63-01B.
790 $a 0084
790 1 0 $a Gilliland, D. Gary, $e advisor
791 $a Ph.D.
792 $a 2002
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3038468