Gravin is a transitory effector of polo-like kinase 1 during cell division.

The mitogenic and second-messenger signals that promote cell proliferation often proceed through multienzyme complexes. The kinase-anchoring protein Gravin integrates cAMP and calcium/phospholipid signals at the plasma membrane by sequestering protein kinases A and C with G protein-coupled receptors. In this report we define a role for Gravin as a temporal ...
organizer of phosphorylation-dependent protein-protein interactions during mitosis. Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis. Fluorescent live-cell imaging reveals that cells depleted of Gravin exhibit mitotic defects that include protracted prometaphase and misalignment of chromosomes. Moreover, a Gravin T766A phosphosite mutant that is unable to interact with Plk1 negatively impacts cell proliferation. In situ detection of phospho-T766 Gravin in biopsy sections of human glioblastomas suggests that this phosphorylation event might identify malignant neoplasms.
Mesh Terms:
A Kinase Anchor Proteins, Animals, Cell Cycle Proteins, Cell Division, Cell Proliferation, Humans, Mice, Mitosis, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Tumor Cells, Cultured
Mol Cell
Date: Nov. 30, 2012
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