Skip to main content
. 2013 Mar 28;9(3):e1003004. doi: 10.1371/journal.pcbi.1003004

Figure 5. Differential ZAP-70 affinity and sequential phosphorylation produces ultrasensitivity.

Figure 5

A) The concentration of bound ZAP-70 as a function of the relative concentration of active kinase (E) to phosphatase (F). Shown are the wild-type Inline graphic-chain (Inline graphic123), and additional constructs where all ITAMs are identical (Inline graphic222), switched (Inline graphic321), or where phosphorylation is no longer sequential (Inline graphic123 Random). The Hill numbers (inset) reveal that ultrasensitivity is decreased if ZAP-70 does not exhibit differential affinity (Inline graphic222), if the affinity decreases as the Inline graphic is sequentially phosphorylated (Inline graphic321), or if phosphorylation is no longer sequential. B) Heat map of Hill numbers as a function of the ZAP-70 unbinding rate for ITAM 1 (ZInline graphic) and ITAM 3 (ZInline graphic), where the unbinding rate for ITAM 2 is fixed at 1 s−1. The calculation is performed under sequential phosphorylation. Maximum sensitivity is found in the top left of the heat map, where ZAP-70 binds with the largest affinity to ITAM 1 and with lowest affinity to ITAM 3. The heat map is repeated using an alternate measure of sensitivity in Fig. S3. Note that the heat map colour scheme in panel B is not related to the colour scheme in panel A.