Tyrosine phosphorylation and activation of focal adhesion kinase (p125FAK) by BCR-ABL oncoprotein
| Autor: | A, Gotoh, K, Miyazawa, K, Ohyashiki, T, Tauchi, H S, Boswell, H E, Broxmeyer, K, Toyama |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Stem Cell Factor
Cytochalasin D Fusion Proteins bcr-abl Gene Expression Protein-Tyrosine Kinases Transfection Recombinant Proteins Cell Line Enzyme Activation Mice Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Leukemia Myelogenous Chronic BCR-ABL Positive Proto-Oncogenes Tumor Cells Cultured Animals Humans Interleukin-3 Phosphorylation Phosphotyrosine Proto-Oncogene Proteins c-abl Cell Adhesion Molecules Cell Division |
| Zdroj: | Experimental hematology. 23(11) |
| ISSN: | 0301-472X |
| Popis: | Focal adhesion kinase (p125FAK; FAK) is a protein tyrosine kinase that is tyrosine-phosphorylated in response to v-src-mediated transformation, cell adhesion, and stimulation with neuropeptides. To elucidate a possible functional relationship between FAK and BCR-ABL oncoprotein detected in Philadelphia chromosome-positive (Ph+) leukemias, we investigated the tyrosine phosphorylation state of FAK in a murine growth factor-dependent cell line and in its stable human bcr-abl cDNA transfectant. In interleukin-3 (IL-3)-dependent NFS/N1.H7 cells, tyrosine phosphorylation of FAK was not detected after stimulation with either IL-3 or Steel factor (SLF), both of which involve Ras-mediated signaling pathways. However, stable gene transfection with p210bcr-abl cDNA into H7 cells made these cells growth factor-independent for proliferation and resulted in constitutive tyrosine phosphorylation and kinase activation of FAK. Constitutive phosphorylation and activation of FAK was also observed in all Ph+ leukemia cell lines examined--that is, K562, TS9;22, and YS9;22, which express p210BCR-ABL, and NALM-21 and OM9;22, which express p185BCR-ABL. Ph-negative (Ph-) cell lines, such as MO7e and JM, did not show any detectable tyrosine phosphorylation of FAK. FAK phosphorylation in BCR-ABL-expressing cells was inhibited in a dose-dependent manner by cytochalasin D, a reagent that disrupts the intracellular network of actin filaments. However, no suppression of kinase activity or protein expression of BCR-ABL was observed after treatment with cytochalasin D. A physical association between BCR-ABL and FAK was not apparent. These data suggest that BCR-ABL may be involved in the activation of FAK. Moreover, FAK may be distinct from components in Ras-mediated signaling cascades that are activated by stimulation of myeloid cells with various cytokines. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|