Abstract
Integrin crosslinking on human B cells induces tyrosine phosphorylation of a set of proteins ranging from 105 to 130 kDa, among which is the focal adhesion kinase p125(FAK). Here we show that the c-CBL protooncogene product p120(c-CBL) is a component of these substrates. β1 integrin stimulation of p120(c-CBL) phosphorylation was observed in both transformed and normal human B cells, and was inbibited by prior treatment of cells with cytochalasin B, which disrupts the actin network. In contrast, tyrosine phosphorylation of p120(c-CBL) following crosslinking of the B cell antigen receptor (BCR) was not affected by cytochalasin B. Integrin stimulation of the promegakaryocytic cell line MO7e also led to a cytoskeleton-dependent tyrosine phosphorylation of p120(c-CBL). In MO7e cells, this stimulation was induced by ligation of either β1 or β2 integrin, whereas only by ligation of β1 integrin in B cells. Tyrosine phosphorylation of p120(c-CBL) links phosphatidylinositol-3 kinase (pI-3K) with the BCR signalling machinery. Although the p85 subunit of PI-3K was increased in p120(c-CBL) immunoprecipitates from BCR-stimulated B cells, this association was only minimally increased by β1 integrin ligation. the function of p120(c-CBL) remains unknown; however, its interactions in vitro and in vivo with Src homology 2 and 3 (SH2 and SH3) domain-containing proteins suggest that p120(c-CBL) has a significant function in signal transduction pathways, and therefore may play a role in integrin signalling in lymphoid and hematopoietic cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 45-50 |
| Number of pages | 6 |
| Journal | Experimental Hematology |
| Volume | 25 |
| Issue number | 1 |
| State | Published - 1997 |
| Externally published | Yes |
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Keywords
- B cells
- cbl
- integrin
- tyrosine phosphorylation
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Genetics
- Hematology
- Oncology
- Transplantation
Cite this
Tyrosine phosphorylation of the product of the c-cbl protooncogenesis induced after integrin stimulation. / Manie, S. N.; Sattler, M.; Astier, A.; Phifer, J. S.; Canty, T.; Morimoto, C.; Druker, Brian; Salgia, R.; Griffin, J. D.; Freedman, A. S.
In: Experimental Hematology, Vol. 25, No. 1, 1997, p. 45-50.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tyrosine phosphorylation of the product of the c-cbl protooncogenesis induced after integrin stimulation
AU - Manie, S. N.
AU - Sattler, M.
AU - Astier, A.
AU - Phifer, J. S.
AU - Canty, T.
AU - Morimoto, C.
AU - Druker, Brian
AU - Salgia, R.
AU - Griffin, J. D.
AU - Freedman, A. S.
PY - 1997
Y1 - 1997
N2 - Integrin crosslinking on human B cells induces tyrosine phosphorylation of a set of proteins ranging from 105 to 130 kDa, among which is the focal adhesion kinase p125(FAK). Here we show that the c-CBL protooncogene product p120(c-CBL) is a component of these substrates. β1 integrin stimulation of p120(c-CBL) phosphorylation was observed in both transformed and normal human B cells, and was inbibited by prior treatment of cells with cytochalasin B, which disrupts the actin network. In contrast, tyrosine phosphorylation of p120(c-CBL) following crosslinking of the B cell antigen receptor (BCR) was not affected by cytochalasin B. Integrin stimulation of the promegakaryocytic cell line MO7e also led to a cytoskeleton-dependent tyrosine phosphorylation of p120(c-CBL). In MO7e cells, this stimulation was induced by ligation of either β1 or β2 integrin, whereas only by ligation of β1 integrin in B cells. Tyrosine phosphorylation of p120(c-CBL) links phosphatidylinositol-3 kinase (pI-3K) with the BCR signalling machinery. Although the p85 subunit of PI-3K was increased in p120(c-CBL) immunoprecipitates from BCR-stimulated B cells, this association was only minimally increased by β1 integrin ligation. the function of p120(c-CBL) remains unknown; however, its interactions in vitro and in vivo with Src homology 2 and 3 (SH2 and SH3) domain-containing proteins suggest that p120(c-CBL) has a significant function in signal transduction pathways, and therefore may play a role in integrin signalling in lymphoid and hematopoietic cells.
AB - Integrin crosslinking on human B cells induces tyrosine phosphorylation of a set of proteins ranging from 105 to 130 kDa, among which is the focal adhesion kinase p125(FAK). Here we show that the c-CBL protooncogene product p120(c-CBL) is a component of these substrates. β1 integrin stimulation of p120(c-CBL) phosphorylation was observed in both transformed and normal human B cells, and was inbibited by prior treatment of cells with cytochalasin B, which disrupts the actin network. In contrast, tyrosine phosphorylation of p120(c-CBL) following crosslinking of the B cell antigen receptor (BCR) was not affected by cytochalasin B. Integrin stimulation of the promegakaryocytic cell line MO7e also led to a cytoskeleton-dependent tyrosine phosphorylation of p120(c-CBL). In MO7e cells, this stimulation was induced by ligation of either β1 or β2 integrin, whereas only by ligation of β1 integrin in B cells. Tyrosine phosphorylation of p120(c-CBL) links phosphatidylinositol-3 kinase (pI-3K) with the BCR signalling machinery. Although the p85 subunit of PI-3K was increased in p120(c-CBL) immunoprecipitates from BCR-stimulated B cells, this association was only minimally increased by β1 integrin ligation. the function of p120(c-CBL) remains unknown; however, its interactions in vitro and in vivo with Src homology 2 and 3 (SH2 and SH3) domain-containing proteins suggest that p120(c-CBL) has a significant function in signal transduction pathways, and therefore may play a role in integrin signalling in lymphoid and hematopoietic cells.
KW - B cells
KW - cbl
KW - integrin
KW - tyrosine phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=0031042152&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031042152&partnerID=8YFLogxK
M3 - Article
VL - 25
SP - 45
EP - 50
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 1
ER -