TY - JOUR
T1 - Cdk5-mediated phosphorylation regulates phosphatidylinositol 4-phosphate 5-kinase type i γ90 activity and cell invasion
AU - Li, Liqing
AU - Kolodziej, Tomasz
AU - Jafari, Naser
AU - Chen, Jing
AU - Zhu, Haining
AU - Rajfur, Zenon
AU - Huang, Cai
N1 - Funding Information:
This work was supported by American Cancer Society Research Scholar Grant RSG-13-184-01CSM (to C.H.) and U.S. National Institutes of Health, National Institute of General Medical Sciences Grant R01 GM122994 (to C.H.). The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
PY - 2019/1
Y1 - 2019/1
N2 - Phosphatidylinositol 4-phosphate 5-kinase type I g (PIPKIγ90) regulates cell migration, invasion, and metastasis. However, it is unknown how cellular signals regulate those processes. Here, we show that cyclindependent kinase 5 (Cdk5), a protein kinase that regulates cell migration and invasion, phosphorylates PIPKIγ90 at S453, and that Cdk5-mediated PIPKIγ90 phosphorylation is essential for cell invasion. Moreover, Cdk5-mediated phosphorylation down-regulates the activity of PIPKIγ90 and the secretion of fibronectin, an extracellular matrix protein that regulates cell migration and invasion. Furthermore, inhibition of PIPKIg activity with the chemical inhibitor UNC3230 suppresses fibronectin secretion in a dose-dependent manner, whereas depletion of Cdk5 enhances fibronectin secretion. With total internal reflection fluorescence microscopy, we found that secreted fibronectin appears as round dots, which colocalize with Tks5 and CD9 but not with Zyxin. These data suggest that Cdk5-mediated PIPKIγ90 phosphorylation regulates cell invasion by controlling PIPKIγ90 activity and fibronectin secretion.
AB - Phosphatidylinositol 4-phosphate 5-kinase type I g (PIPKIγ90) regulates cell migration, invasion, and metastasis. However, it is unknown how cellular signals regulate those processes. Here, we show that cyclindependent kinase 5 (Cdk5), a protein kinase that regulates cell migration and invasion, phosphorylates PIPKIγ90 at S453, and that Cdk5-mediated PIPKIγ90 phosphorylation is essential for cell invasion. Moreover, Cdk5-mediated phosphorylation down-regulates the activity of PIPKIγ90 and the secretion of fibronectin, an extracellular matrix protein that regulates cell migration and invasion. Furthermore, inhibition of PIPKIg activity with the chemical inhibitor UNC3230 suppresses fibronectin secretion in a dose-dependent manner, whereas depletion of Cdk5 enhances fibronectin secretion. With total internal reflection fluorescence microscopy, we found that secreted fibronectin appears as round dots, which colocalize with Tks5 and CD9 but not with Zyxin. These data suggest that Cdk5-mediated PIPKIγ90 phosphorylation regulates cell invasion by controlling PIPKIγ90 activity and fibronectin secretion.
KW - Cell migration
KW - Extracellular matrix protein
KW - Fibronectin
KW - Phosphatidylinositol kinase
KW - Secretion
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U2 - 10.1096/fj.201800296R
DO - 10.1096/fj.201800296R
M3 - Article
C2 - 30040488
AN - SCOPUS:85059242030
SN - 0892-6638
VL - 33
SP - 631
EP - 642
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -