Mukhopadhyay2013 - T cell receptor proximal signaling reveals emergent ultrasensitivity
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ABSTRACT:
Mukhopadhyay2013 - T cell receptor proximal
signaling reveals emergent ultrasensitivity
This model is described in the article:
Systems model of T cell
receptor proximal signaling reveals emergent
ultrasensitivity.
Mukhopadhyay H, Cordoba SP, Maini
PK, van der Merwe PA, Dushek O.
PLoS Comput. Biol. 2013; 9(3):
e1003004
Abstract:
Receptor phosphorylation is thought to be tightly regulated
because phosphorylated receptors initiate signaling cascades
leading to cellular activation. The T cell antigen receptor
(TCR) on the surface of T cells is phosphorylated by the kinase
Lck and dephosphorylated by the phosphatase CD45 on multiple
immunoreceptor tyrosine-based activation motifs (ITAMs).
Intriguingly, Lck sequentially phosphorylates ITAMs and ZAP-70,
a cytosolic kinase, binds to phosphorylated ITAMs with
differential affinities. The purpose of multiple ITAMs, their
sequential phosphorylation, and the differential ZAP-70
affinities are unknown. Here, we use a systems model to show
that this signaling architecture produces emergent
ultrasensitivity resulting in switch-like responses at the
scale of individual TCRs. Importantly, this switch-like
response is an emergent property, so that removal of multiple
ITAMs, sequential phosphorylation, or differential affinities
abolishes the switch. We propose that highly regulated TCR
phosphorylation is achieved by an emergent switch-like response
and use the systems model to design novel chimeric antigen
receptors for therapy.
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MODEL1604100000.
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SUBMITTER: 
Omer Dushek
PROVIDER: MODEL1604100000 | BioModels | 2016-11-03
REPOSITORIES: BioModels
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