Abstract
Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed, U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 3013-3023 |
| Number of pages | 11 |
| Journal | EMBO Journal |
| Volume | 18 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Jun 1 1999 |
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Keywords
- Cell motility and adhesion
- Cytoskeleton
- Myelomonocytic differentiation
- Src kinases
- Urokinase receptor signalling
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence. / Chiaradonna, Ferdinando; Fontana, Laura; Iavarone, Carlo; Carriero, M. Vincenza; Scholz, Glen; Barone, M. Vittoria; Stoppelli, M. Patrizia.
In: EMBO Journal, Vol. 18, No. 11, 01.06.1999, p. 3013-3023.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence
AU - Chiaradonna, Ferdinando
AU - Fontana, Laura
AU - Iavarone, Carlo
AU - Carriero, M. Vincenza
AU - Scholz, Glen
AU - Barone, M. Vittoria
AU - Stoppelli, M. Patrizia
PY - 1999/6/1
Y1 - 1999/6/1
N2 - Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed, U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.
AB - Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed, U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.
KW - Cell motility and adhesion
KW - Cytoskeleton
KW - Myelomonocytic differentiation
KW - Src kinases
KW - Urokinase receptor signalling
UR - http://www.scopus.com/inward/record.url?scp=0033153319&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033153319&partnerID=8YFLogxK
U2 - 10.1093/emboj/18.11.3013
DO - 10.1093/emboj/18.11.3013
M3 - Article
C2 - 10357814
AN - SCOPUS:0033153319
VL - 18
SP - 3013
EP - 3023
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 11
ER -