CD28 signaling events

CD28 signaling events. CD28 associates with several intracellular signaling proteins (). PI3K generates D-3 lipids, which consequently recruit PDK1. PDK1 can activate PKB/AKT, PKC-θ and S6K by phosphorylation, while PKB phosphorylates numerous proteins, like BAD, mTOR and GSK3. Further, PI3K interacts with SNX9, which in turn interacts with WASP and thus can regulate actin cytoskeleton (not depicted). Similarly, another CD28 binding partner, Grb2 can bind SOS, an activator of GTPase Ras, and another guanine nucleotide exchange factor Vav1. Once activated by tyrosine phosphorylation, Vav1 activates Rac and cdc42 leading to an activation of JNK, p38 (not depicted) and actin cytoskeleton remodelling. Grb-2 binding to the YMNM motif and Vav1 is important in the activation of the NFκB pathway. Similarly, FLNa binding to the PPAYP motif is needed for activation of the NFκB pathway and can regulate actin cytoskeleton. The role of CD28 interaction with Lck and Itk and its consequences remain to be elucidated in more detail (not depicted). BAD, Bcl-2-antagonist of cell death; cdc42, cell-division cycle 42; FLNa, filamin-A; FOXO, forkhead transcription factor O; Grb2, growth-factor receptor-bound protein; GSK, glycogen synthase kinase 3; IKK, IκB kinase; Lck, lymphocyte-specific protein tyrosine kinase; mTOR, mammalian target of rapamycin; PDK1, phosphoinositide-dependent kinase 1; PI3K, phosphatidylinositol 3-kinase; PKB, protein kinase B; PKC-θ, protein kinase C u; Rac1, Ras-related C3 botulinum toxin substrate 1; Ras, p21/Rat sarcoma; S6K, S6 kinase.

Publication

CD28 co-signaling in the adaptive immune response. (2010) Pavel Riha, et al. Self Nonself. 2010 Jul-Sep;1(3):231-240. Figure: F5. Homo sapiens

Disease mentions