The term Kinase tyrosine-based inhibitory motif (KTIM) was coined by a group of immunology researchers from
McGill University,
Montreal, Quebec, Canada
[Abu-Dayyeh I. et al.,2008. PLoS Negl Trop Dis 2(12): e305. ] in 2008 to represent any
immunoreceptor tyrosine-based inhibitory-like
sequence motif
In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''As ...
, with the consensus sequence I/V/L/SxYxxL/V, found in a
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
and regulating its activity.
One major way in which cells respond to stimuli is through signal transduction pathways, whereby a ligand binds to a receptor, causing conformational changes that lead to a cascade of events in intracellular signalling molecules. This ultimately ends up in the translocation of transcription factors to the nucleus altering the expression of target genes, therefore affecting specific cellular functions. One way activation signals can be counteracted is through the triggering of different receptors bearing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tails.
Several
transmembrane receptors are negatively regulated through recruiting
cytosolic
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrio ...
SH2 domain-containing
proteins such as
SHP-1 to
immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that they possess. ITIM-like motifs (KTIMs) were shown to exist in non-receptor proteins and to play a key role in their regulation.
Difference between KTIM and ITIM
The main difference between ITIM and KTIM is that KTIM was shown to be found in a cytosolic protein (IL-1 receptor-associated Kinase 1 (IRAK-1)) and not in a transmembrane protein such as the case with ITIMs.
KTIM function
KTIMs are speculated to play a regulatory role in the negative regulation of many kinases in addition to IRAK-1, and can thus represent a novel regulatory mechanism in a wide range of cellular kinases.
[Abu-Dayyeh I. et al.,2010. Dev. Comp. Immunol.,34(5):481-484, :] The mode of action of KTIMs is similar to ITIMs and involves recruiting SH2 domain-containing proteins such as SHP-1.
References
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Immunology