PathwayStep6500 PathwayStep6501 PathwayStep6515 PathwayStep6508 PathwayStep6503 PathwayStep6502 CD28 homodimer binds B7-1 homodimer CD28 homodimer binds B7-2 monomer Phosphorylation of CD28 Gads binds CD28 CD28 dependent Vav1 pathway CD28 co-stimulation Authored: Garapati, P V, 2008-12-16 11:12:19 Edited: Garapati, P V, 2008-12-16 11:12:19 GENE ONTOLOGYGO:0031295 In naive T cells, CD28 costimulation enhances cell cycle entry, potently stimulates expression of both the mitogenic lymphokine interleukin-2 (IL-2) and its receptor, and stimulates the activation of an antiapoptotic program. CD28 engages with one or both members of the B7 receptor family, B7.1 and B7.2. Upon ligand binding the tyrosines and proline-rich motifs present in the cytoplasmic tail of CD28 are phosphorylated by Lck or Fyn. Upon phosphorylation CD28 recruits and induces phosphorylation and activation of a more restricted set of intracellular signaling components that, together with those mobilized by the TCR, contribute to convert membrane-based biochemical and biophysical changes into gene activation events. Proteins like PI3K, Vav-1, Tec and Itk kinases, AKT, and the Dok-1 adaptor have been identified as elements of the CD28 signaling pathway by biochemical or genetic approaches or both. Pubmed12165654 Pubmed8609386 Pubmed8649453 Reactome Database ID Release 43389356 Reactome, http://www.reactome.org ReactomeREACT_19183 Reviewed: Bluestone, JA, Esensten, J, 2009-06-01 18:47:33 CD28 dependent PI3K/Akt signaling