The term Kinase tyrosine-based inhibitory motif (KTIM) was coined by a group of immunology researchers from

McGill University McGill University (French: Université McGill) is an English-language public research university in Montreal, Quebec, Canada. Founded in 1821 by royal charter,Frost, Stanley Brice. ''McGill University, Vol. I. For the Advancement of Learning, ...

Montreal, Quebec Montreal is the List of towns in Quebec, largest city in the Provinces and territories of Canada, province of Quebec, the List of the largest municipalities in Canada by population, second-largest in Canada, and the List of North American cit ...

, 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 ''A ...

, 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 receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptor (biochemistry), receptors that are embedded in the cell membrane, plasma membrane of cell (biology), cells. They act in cell signaling by receiving (binding to) ex ...

s 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 mitochondri ...

SH2 domain The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains bind to phosphorylated tyrosine residues on other proteins, ...

-containing

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s such as

SHP-1 Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the ''PTPN6'' gene. Function The protein encoded by this gene is a member ...

immunoreceptor tyrosine-based inhibitory motif An immunoreceptor tyrosine-based inhibitory motif (ITIM), is a conserved sequence of amino acids that is found intracellularly in the cytoplasmic domains of many inhibitory receptors of the non-catalytic tyrosine-phosphorylated receptor family fou ...

s (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

{{reflist Immunology