Contributor:
Bhandari, Deepali;
Lopez-Sanchez, Inmaculada;
To, Andrew;
Lo, I-Chung;
Aznar, Nicolas;
Leyme, Anthony;
Gupta, Vijay;
Niesman, Ingrid;
Maddox, Adam L.;
Garcia-Marcos, Mikel;
Farquhar, Marilyn G.;
Ghosh, Pradipta
imprint:
Proceedings of the National Academy of Sciences, 2015
Published in:
Proceedings of the National Academy of Sciences, 112 (2015) 35
Language:
English
DOI:
10.1073/pnas.1514157112
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<jats:title>Significance</jats:title>
<jats:p>The guanine nucleotide exchange factor (GEF) GIV/Girdin has previously been shown to trigger noncanonical activation of trimeric G proteins in response to multiple chemical stimuli at the plasma membrane and at various locations within cells. In this work we identified a single phosphoevent and pinpointed cyclin-dependent kinase 5 (CDK5) as the responsible kinase that activates GIV's GEF function and initiates noncanonical G protein signaling via GIV. These studies provide evidence that CDK5 is essential for maximal activation of GIV-GEF in cells and insights into a hitherto unrecognized crosstalk between CDK5 and G proteins via GIV. Such crosstalk may shape migration–proliferation dichotomy during several physiological and pathological scenarios such as wound healing and cancer metastasis.</jats:p>