The Dictyostelium GSK3 kinase GlkA coordinates signal relay and chemotaxis in response to growth conditions

Developmental biology

Zhouxin Shen^1¹  Jesus Lacal Romero^1² 

[1] JadeBio, Inc., 505 Coast Boulevard South Suite 206, La Jolla, CA 92037, USA^2;Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA^1

关键词: GlkA;    glycogen synthase kinase-like kinase A;    PI(3,4,5)P3;    phosphatidylinositol (3,4,5)-triphosphate;    MyoII;    Myosin II;    AL;    activation loop;    HM;    hydrophobic motif;    RBD;    Ras binding domain;    iTRAQ;    isobaric tags for relative and absolute quantification;    DIAS;    Dynamic Image Analysis System;    GSK3;    Chemotaxis;    Cytoskeleton;    cAMP;    Ras;    Proteomics;   

DOI  :  10.1016/j.ydbio.2018.01.007

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

GSK3 plays a central role in orchestrating key biological signaling pathways, including cell migration. Here, we identify GlkA as a GSK3 family kinase with functions that overlap with and are distinct from those of GskA. We show that GlkA, as previously shown for GskA, regulates the cell's cytoskeleton through MyoII assembly and control of Ras and Rap1 function, leading to aberrant cell migration. However, there are both qualitative and quantitative differences in the regulation of Ras and Rap1 and their downstream effectors, including PKB, PKBR1, and PI3K, with glkA- cells exhibiting a more severe chemotaxis phenotype than gskA- cells. Unexpectedly, the severe glkA- phenotypes, but not those of gskA-, are only exhibited when cells are grown attached to a substratum but not in suspension, suggesting that GlkA functions as a key kinase of cell attachment signaling. Using proteomic iTRAQ analysis we show that there are quantitative differences in the pattern of protein expression depending on the growth conditions in wild-type cells. We find that GlkA expression affects the cell's proteome during vegetative growth and development, with many of these changes depending on whether the cells are grown attached to a substratum or in suspension. These changes include key cytoskeletal and signaling proteins known to be essential for proper chemotaxis and signal relay during the aggregation stage of Dictyostelium development.

【 授权许可】

CC BY