Repository landing page

We are not able to resolve this OAI Identifier to the repository landing page. If you are the repository manager for this record, please head to the Dashboard and adjust the settings.


<p>Following TCR-pMHC binding, Itk molecules are bound by the LAT signalosome via SLP-76 (not shown). Itk molecules (monomers or dimers, blue diamonds), bind the membrane lipid PIP<sub>3</sub> with low affinity through their PH domains. PIP<sub>3</sub> bound Itk phosphorylates and thereby activates LAT-bound PLCγ1. Activated PLCγ1 then hydrolyzes the membrane lipid PIP<sub>2</sub> into the soluble second messenger IP<sub>3</sub>, a key mediator of Ca<sup>2+</sup> mobilization. IP<sub>3</sub> 3-kinase B (ItpkB) converts IP<sub>3</sub> into IP<sub>4</sub> (red filled circle). For our <i>in silico</i> models, we simplified this series of reactions, encircled by the orange oval, into a single second order reaction where PIP<sub>3</sub> bound Itk converts PIP<sub>2</sub> into IP<sub>4</sub>. In models M1–M4 and M7, IP<sub>4</sub> modifies the Itk PH domain (denoted as Itk<sup>C</sup>, purple diamonds) to promote PIP<sub>3</sub> and IP<sub>4</sub> binding to the Itk PH domain. At the onset of the signaling, when the concentration of IP<sub>4</sub> is smaller than that of PIP<sub>3</sub>, IP<sub>4</sub> helps Itk<sup>C</sup> to bind to PIP<sub>3</sub> (left lower panel). However, as the concentration of IP<sub>4</sub> is increased at later times, IP<sub>4</sub> outcompetes PIP<sub>3</sub> for binding to Itk<sup>C</sup> and sequesters Itk<sup>C</sup> to the cytosol (right lower panel). In models M5/M6, IP<sub>4</sub> and PIP<sub>3</sub> do not augment each other’s binding to Itk. However, IP<sub>4</sub> still outcompetes PIP<sub>3</sub> for Itk PH domain binding when the number of IP<sub>4</sub> molecules becomes much larger than that of PIP<sub>3</sub> molecules at later times.</p

Similar works

Full text



Last time updated on 12/02/2018

This paper was published in FigShare.

Having an issue?

Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.