TY - JOUR
T1 - The multidomain protooncogenic protein c-Cbl binds to tubulin and stabilizes microtubules
AU - Teckchandani, Anjali M.
AU - Birukova, Anna A.
AU - Tar, Krisztina
AU - Verin, Alexander D.
AU - Tsygankov, Alexander Y.
N1 - Funding Information:
The authors would like to thank Drs. Band and Yarden for their kind gift of reagents and G. Harvey for his excellent editorial help. This study was supported by grants from the National Institutes of Health (CA78499 to A.Y.T. and HL67307 and HL68062 to A.D.V.).
PY - 2005/5/15
Y1 - 2005/5/15
N2 - The protooncogenic protein c-Cbl is known to regulate the actin cytoskeleton. In this study, we present results indicating that c-Cbl can also regulate the microtubular network. We have shown that c-Cbl binds to tubulin and microtubules through its tyrosine kinase binding (TKB) domain. However, the character of the interactions described in this report is novel, since the G306E mutation, which disrupts the ability of c-Cbl's TKB to bind to tyrosine-phosphorylated proteins, does not affect the observed interaction between c-Cbl and microtubules. Furthermore, overexpression of c-Cbl in human pulmonary artery endothelial cells and COS-7 cells leads to microtubule stabilization. We demonstrate that this effect of c-Cbl is mediated by TKB, and, like c-Cbl binding to microtubules, is independent of the ability of TKB to bind to tyrosine-phosphorylated proteins. Finally, we have shown that c-Cbl directly polymerizes microtubules in vitro, and that TKB is necessary and sufficient for this effect of c-Cbl. In this last phenomenon, as well as in the previous ones, the effect of TKB is not sensitive to the inactivating G306E mutation. Overall, the results presented in this report suggest a novel function for c-Cbl-microtubule binding and stabilization.
AB - The protooncogenic protein c-Cbl is known to regulate the actin cytoskeleton. In this study, we present results indicating that c-Cbl can also regulate the microtubular network. We have shown that c-Cbl binds to tubulin and microtubules through its tyrosine kinase binding (TKB) domain. However, the character of the interactions described in this report is novel, since the G306E mutation, which disrupts the ability of c-Cbl's TKB to bind to tyrosine-phosphorylated proteins, does not affect the observed interaction between c-Cbl and microtubules. Furthermore, overexpression of c-Cbl in human pulmonary artery endothelial cells and COS-7 cells leads to microtubule stabilization. We demonstrate that this effect of c-Cbl is mediated by TKB, and, like c-Cbl binding to microtubules, is independent of the ability of TKB to bind to tyrosine-phosphorylated proteins. Finally, we have shown that c-Cbl directly polymerizes microtubules in vitro, and that TKB is necessary and sufficient for this effect of c-Cbl. In this last phenomenon, as well as in the previous ones, the effect of TKB is not sensitive to the inactivating G306E mutation. Overall, the results presented in this report suggest a novel function for c-Cbl-microtubule binding and stabilization.
KW - Acetylation
KW - Endothelial cells
KW - Microtubules
KW - Polymerization
KW - Stabilization
KW - Tubulin
KW - c-Cbl
UR - http://www.scopus.com/inward/record.url?scp=18844455052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18844455052&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2005.02.014
DO - 10.1016/j.yexcr.2005.02.014
M3 - Article
C2 - 15878338
AN - SCOPUS:18844455052
SN - 0014-4827
VL - 306
SP - 114
EP - 127
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -