˜˜°˛˝˙˙ˆmIgMTCR Ig°Ig˛Tyrosine kinases Adaptors and scaffold proteins Phospholipases and lipid kinases GTPases, serine/threonine kinases, and phosphatases Transcription factors, cytoskeletal changes, adhesion, metabolism
Fig. 7.28 Summary of antigen receptor signaling pathways. as outlined in this section, the signal transduction pathways downstream of the T-cell and B-cell receptors occur in an orchestrated series of stages involving many categories of proteins that produce widespread changes in the cells. The first detectable events following antigen receptor stimulation are the activation of tyrosine kinases. following this, adaptor proteins and scaffolds are modified, recruiting phospholipases and lipid kinases to the activated receptor complexes. The next level of signaling amplifies these earlier stages by activating multiple small GTpases, serine/threonine kinases, and protein phosphatases. Together, these lead to transcription factor activation, cytoskeletal changes, and increases in cellular adhesion and metabolism, all of which contribute to T-and B-cell activation.
membrane-bound antigen, B-cell receptor signaling also produces an immune synapse that localizes signaling complexes to the cell–cell interface. One key function of the immune synapse in B cells is to promote antigen uptake by the B cell, a prerequisite to presenting that antigen in the form of peptide:MHC complexes to CD4 T cells.
B-cell receptor signaling also induces metabolic changes in activated B cells. As is the case for T cells, this response is dependent on the action of PI 3-kinase, whose activation leads to formation of the membrane phosphoinositide PI(3,4,5)P3 at the site of the activated B-cell receptor. This response is augmented by combined signaling through the B-cell receptor plus the B-cell co-receptor complex of CD19/CD21/CD81. PI(3,4,5)P3 recruits Akt, which is then phosphorylated and activated, leading to downstream activation of mTOR, as well as additional Akt-dependent pathways promoting cell survival and proliferation (see Fig. 7.27).
Summary.