The TCR activates cytoplasmic kinases (including Lck, ZAP-70, and PLCγ), which signal via intermediates to induce the activation of members of three distinct families of transcription factors, Rel, activator protein–1 (AP1), and nuclear factor of activated T cells (NFAT). These transcription factors then coordinate the expression of the genes encoding IL-2 and the subunits of IL-2R, thereby rendering the cell competent to progress through the cell cycle. Heteromeric cytokine receptors, here represented by IL-2R, are composed of two or three distinct transmembrane chains. Binding of the cytokine to the external receptor chain domains brings the cytoplasmic domains into close enough proximity for their respective receptor-associated JAK molecules to initiate signaling. Subsequently, the activated STAT dimers translocate to the nucleus and initiate transcription of genes encoding proteins such as cyclin D₂ (Cyc D) to promote progression beyond the R-point and also genes encoding cell-survival proteins, such as Bcl-X_L. By comparison, homomeric receptors already have the same bound JAK molecules in close proximity, and ligand binding readily initiates signaling by promoting transphosphorylation of JAK2, the receptor chains, and eventually STAT5. G-CSFR, G-CSF receptor; EpoR, erythropoietin receptor; TpoR, thrombopoietin receptor.