Abstract
Focal adhesion kinase (p125(FAK); 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 Pas-mediated signaling pathways. However, stable gene transfection with p210(bcr-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 PAK was also observed in all Ph+ leukemia cell lines examined-that is, K562, TS9;22, and YS9;22, which express p210(BCR-ABL), and NALM-21 and YS9;22, which express p185(BCR-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 Pas-mediated signaling cascades that are activated by stimulation of myeloid cells with various cytokines.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1153-1159 |
| Number of pages | 7 |
| Journal | Experimental Hematology |
| Volume | 23 |
| Issue number | 11 |
| State | Published - 1995 |
| Externally published | Yes |
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Keywords
- BCR-ABL
- Focal adhesion kinase
- Signal transduction
- Tyrosine phosphorylation
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Genetics
- Hematology
- Oncology
- Transplantation
Cite this
Tyrosine phosphorylation and activation of focal adhesion kinase (p125(FAK)) by BCR-ABL oncoprotein. / Gotoh, A.; Miyazawa, K.; Ohyashiki, K.; Tauchi, T.; Boswell, H.; Broxmeyer, Hal; Toyama, K.
In: Experimental Hematology, Vol. 23, No. 11, 1995, p. 1153-1159.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tyrosine phosphorylation and activation of focal adhesion kinase (p125(FAK)) by BCR-ABL oncoprotein
AU - Gotoh, A.
AU - Miyazawa, K.
AU - Ohyashiki, K.
AU - Tauchi, T.
AU - Boswell, H.
AU - Broxmeyer, Hal
AU - Toyama, K.
PY - 1995
Y1 - 1995
N2 - Focal adhesion kinase (p125(FAK); 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 Pas-mediated signaling pathways. However, stable gene transfection with p210(bcr-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 PAK was also observed in all Ph+ leukemia cell lines examined-that is, K562, TS9;22, and YS9;22, which express p210(BCR-ABL), and NALM-21 and YS9;22, which express p185(BCR-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 Pas-mediated signaling cascades that are activated by stimulation of myeloid cells with various cytokines.
AB - Focal adhesion kinase (p125(FAK); 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 Pas-mediated signaling pathways. However, stable gene transfection with p210(bcr-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 PAK was also observed in all Ph+ leukemia cell lines examined-that is, K562, TS9;22, and YS9;22, which express p210(BCR-ABL), and NALM-21 and YS9;22, which express p185(BCR-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 Pas-mediated signaling cascades that are activated by stimulation of myeloid cells with various cytokines.
KW - BCR-ABL
KW - Focal adhesion kinase
KW - Signal transduction
KW - Tyrosine phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=0028889810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028889810&partnerID=8YFLogxK
M3 - Article
C2 - 7556524
AN - SCOPUS:0028889810
VL - 23
SP - 1153
EP - 1159
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 11
ER -