The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival
of Precursor B-acute Lymphoblastic Leukemia Cells

J 2002

The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival of Precursor B-acute Lymphoblastic Leukemia Cells

SARKAR, Sibaji, Marek SVOBODA, Rosalie DE BEAUMONT and Arnold FREEDMAN

Basic information

Original name

The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival of Precursor B-acute Lymphoblastic Leukemia Cells

Name in Czech

Význam AKT a RAFTK kinas v přežívání prekurzorových buněk akutní B-lymfoblastické leukémie zprostředkovaném stimulací B1 integrinů.

Authors

SARKAR, Sibaji (840 United States of America), Marek SVOBODA (203 Czech Republic, guarantor), Rosalie DE BEAUMONT (840 United States of America) and Arnold FREEDMAN (840 United States of America)

Edition

Leukemia and Lymphoma, 2002, 1042-8194

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 1.335

Organization unit

Faculty of Medicine

Keywords in English

Integrin; Leukemia; Kinase; Adhesion

Abstract

ORIG CZ

V originále

In this study, we report that the related adhesion focal tyrosine kinase RAFTK, is an upstream kinase in 1 integrin mediated activation of Akt. Stimulation through 1 integrins by fibronectin reversed apoptosis induced by adriamycin. Inhibitors of phosphatidylinositol 3-kinase (PI3 kinase)/Akt (LY 294002), tyrosine kinases (Herbimycin-A) and the cytotoxic agent adriamycin induced apoptosis of REH cells. 1 integrin ligation induced activation of Akt, and tyrosine phosphorylation of RAFTK and FAK, but not SYK in REH cells. This suggested that RAFTK and FAK activation might be linked to Akt activation. Evidence that RAFTK is a modulator of Akt came from phorbol myristic acetate (PMA) stimulation. RAFTK and Akt were activated but FAK was not. Using fibroblasts from FAK -/ -mice, which express high levels of RAFTK, fibronectin plating enhanced Akt activation. Pretreatment of REH cells with a PI3 kinase/Akt inhibitor LY 294002 did not inhibit RAFTK tyrosine phosphorylation showing that RAFTK is upstream of PI3k/Akt. Further evidence for a link between RAFTK tyrosine phosphorylation and Akt activation was the observation that the p85 subunit of PI3 kinase associated with RAFTK following integrin ligation in REH cells. These results suggest that RAFTK plays an anti-apoptotic role through the activation of Akt.

In Czech

Publikace je pouze v anglickém jazyce.

Citovat

SARKAR, Sibaji, Marek SVOBODA, Rosalie DE BEAUMONT and Arnold FREEDMAN. The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival of Precursor B-acute Lymphoblastic Leukemia Cells. Leukemia and Lymphoma. 2002, vol. 2002, No 8, p. 1663-1671. ISSN 1042-8194.

@article{726203,
   author = {Sarkar, Sibaji and Svoboda, Marek and de Beaumont, Rosalie and Freedman, Arnold},
   article_number = {8},
   keywords = {Integrin; Leukemia; Kinase; Adhesion},
   language = {eng},
   issn = {1042-8194},
   journal = {Leukemia and Lymphoma},
   title = {The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival of Precursor B-acute Lymphoblastic Leukemia Cells},
   volume = {2002},
   year = {2002}
}

TY  - JOUR
ID  - 726203
AU  - Sarkar, Sibaji - Svoboda, Marek - de Beaumont, Rosalie - Freedman, Arnold
PY  - 2002
TI  - The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival of Precursor B-acute Lymphoblastic Leukemia Cells
JF  - Leukemia and Lymphoma
VL  - 2002
IS  - 8
SP  - 1663-1671
EP  - 1663-1671
SN  - 10428194
KW  - Integrin
KW  - Leukemia
KW  - Kinase
KW  - Adhesion
N2  - In this study, we report that the related adhesion focal tyrosine kinase RAFTK, is an upstream kinase in 1 integrin mediated activation of Akt. Stimulation through 1 integrins by fibronectin reversed apoptosis induced by adriamycin. Inhibitors of phosphatidylinositol 3-kinase (PI3 kinase)/Akt (LY 294002), tyrosine kinases (Herbimycin-A) and the cytotoxic agent adriamycin induced apoptosis of REH cells. 1 integrin ligation induced activation of Akt, and tyrosine phosphorylation of RAFTK and FAK, but not SYK in REH cells. This suggested that RAFTK and FAK activation might be linked to Akt activation. Evidence that RAFTK is a modulator of Akt came from phorbol myristic acetate (PMA) stimulation. RAFTK and Akt were activated but FAK was not. Using fibroblasts from FAK -/ -mice, which express high levels of RAFTK, fibronectin plating enhanced Akt activation. Pretreatment of REH cells with a PI3 kinase/Akt inhibitor LY 294002 did not inhibit RAFTK tyrosine phosphorylation showing that RAFTK is upstream of PI3k/Akt. Further evidence for a link between RAFTK tyrosine phosphorylation and Akt activation was the observation that the p85 subunit of PI3 kinase associated with RAFTK following integrin ligation in REH cells. These results suggest that RAFTK plays an anti-apoptotic role through the activation of Akt.
ER  -

SARKAR, Sibaji, Marek SVOBODA, Rosalie DE BEAUMONT and Arnold FREEDMAN. The Role of AKT and RAFTK in Beta1 Integrin Mediated Survival of Precursor B-acute Lymphoblastic Leukemia Cells. \textit{Leukemia and Lymphoma}. 2002, vol.~2002, No~8, p.~1663-1671. ISSN~1042-8194.

Detailed Information on Publication Record