I am reading a journal paper about the insulin receptor (IR). The insulin receptor is a receptor tyrosine kinase, and upon ligand binding, undergoes autophosphorylation of intracellular tyrosine residues.

In this paper, they have shown that major histocompatibility class I (MHC-I) regulates the phosphorylation of the insulin receptor by inducing conformational changes in the intracellular domains of IR.

One thing that I have seen is that this paper uses the terms "tonic activation", "tonic inhibition" and "tonic brake". For example, they have the following statements:

Insulin receptor signaling is tonically activated in MHCI-deficient mice, and inhibiting insulin receptor signaling rescues synapse number in these transgenic mice, suggesting that loss of MHCI relieves a tonic brake on insulin receptor signaling to increase synapse density.


Neurons with reduced cell surface MHCI are profoundly insulin insensitive at the level of the receptor, due to ongoing tonic insulin receptor activation.

I am not sure, in the context of receptor tyrosine kinases, what the terms tonic activation/inhibition/brake mean. I have searched online, but haven't been able to find a precise definition.

Any insights are appreciated.


1 Answer 1


Tonic in this context is the opposite of "phasic". Tonic receptor activation is slow or constant or the level of activity at "rest", whereas phasic is fast or in response to some stimulus.

When talking about an insulin receptor, if someone mentions an "increase in tonic activation" they probably mean that receptor activity (in this case, kinase activity or probability of phosphorylation) at a constant, low insulin concentration is higher. You might observe this because of a stronger affinity for insulin, or by a mechanism that allows the receptor to be active even without binding its ligand. The latter seems to be indicated if they are talking about a cell that's insulin insensitive - if the receptors are already active at rest there is nothing for the ligand to do.

A "tonic brake" would be something that inhibits or opposes the tonic activity of something; in the case of phosphorylation that could be something that either prevents phosphorylation or causes dephosphorylation.


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