TY - JOUR
T1 - Phosphorylation of CLIP-170 by Plk1 and CK2 promotes timely formation of kinetochore-microtubule attachments
AU - Li, Hongchang
AU - Liu, X. Shawn
AU - Yang, Xiaoming
AU - Wang, Yingmin
AU - Wang, Yun
AU - Turner, Jerrold R.
AU - Liu, Xiaoqi
PY - 2010/9/1
Y1 - 2010/9/1
N2 - CLIP-170 is implicated in the formation of kinetochore-microtubule attachments through direct interaction with the dynein/dynactin complex. However, whether this important function of CLIP-170 is regulated by phosphorylation is unknown. Herein, we have identified polo-like kinase 1 (Plk1) and casein kinase 2 (CK2) as two kinases of CLIP-170 and mapped S195 and S1318 as their respective phosphorylation sites. We showed that a CK2 unphosphorylatable mutant lost its ability to bind to dynactin and to localize to kinetochores during prometaphase, indicating that the CK2 phosphorylation of CLIP-170 is involved in its dynactin-mediated kinetochore localization. Furthermore, we provide evidence that Plk1 phosphorylation of CLIP-170 at S195 enhances its association with CK2. Finally, we detected defects in the formation of kinetochore fibres in cells expressing the CLIP-S195A and -S1318A, but not the CLIP-S195E and -S1318D, confirming that Plk1- and CK2-associated phosphorylations of CLIP-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis.
AB - CLIP-170 is implicated in the formation of kinetochore-microtubule attachments through direct interaction with the dynein/dynactin complex. However, whether this important function of CLIP-170 is regulated by phosphorylation is unknown. Herein, we have identified polo-like kinase 1 (Plk1) and casein kinase 2 (CK2) as two kinases of CLIP-170 and mapped S195 and S1318 as their respective phosphorylation sites. We showed that a CK2 unphosphorylatable mutant lost its ability to bind to dynactin and to localize to kinetochores during prometaphase, indicating that the CK2 phosphorylation of CLIP-170 is involved in its dynactin-mediated kinetochore localization. Furthermore, we provide evidence that Plk1 phosphorylation of CLIP-170 at S195 enhances its association with CK2. Finally, we detected defects in the formation of kinetochore fibres in cells expressing the CLIP-S195A and -S1318A, but not the CLIP-S195E and -S1318D, confirming that Plk1- and CK2-associated phosphorylations of CLIP-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis.
KW - kinetochore
KW - microtubule attachment
KW - phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=77956394930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956394930&partnerID=8YFLogxK
U2 - 10.1038/emboj.2010.174
DO - 10.1038/emboj.2010.174
M3 - Article
C2 - 20664522
AN - SCOPUS:77956394930
SN - 0261-4189
VL - 29
SP - 2953
EP - 2965
JO - EMBO Journal
JF - EMBO Journal
IS - 17
ER -