Molecular Medicine Israel

Pinpointing a key player in autoimmunity

Nature Immunology 12, 1113–1118 (2011); Doi: 10.1038/ni.2121
Huai-Chia Chuang, Joung-Liang Lan, Der-Yuan Chen, Chia-Yu Yang, Yi-Ming Chen, Ju-Pi Li, Ching-Yu Huang, Pao-En Liu, Xiaohong Wang & Tse-Hua Tan.
“The kinase
GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T cells”.

A previously elusive activator of immune cells and autoimmunity in mice and humans is identified as the signaling protein GLK.

Autoimmune diseases occur when the immune system mistakenly attacks the body’s own cells. Biologists have been on the hunt for the direct activator of this process since it will provide new therapeutic targets. Now, Tse-Hua Tan at the National Health Research Institutes in Taiwan and colleagues have identified the signaling protein GLK as a key link in a signaling pathway that drives immune cell activation. The researchers also found that dysregulation of this pathway can affect autoimmunity.

T cells of the immune system are activated when a phosphate group is attached to their intracellular protein kinase C-θ (PKC-θ). In mouse T cells, Tan and colleagues revealed that GLK is the enzyme responsible for adding this phosphate group. Combining purified GLK and PKC-θ in a test tube also led to the addition of a phosphate group to PKC-θ. Further experiments showed that GLK-deficient mice had T cells that failed to proliferate in response to antigens, and were resistant to induction of a brain autoimmune disease.

In humans with the autoimmune disease lupus, which targets many organs including the joints and skin, Tan and colleagues found that T cells in their blood contained GLK more frequently than in unaffected individuals. The findings therefore suggest that inhibiting GLK could fight autoimmunity.


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