Ligand binding to type I receptors with a common subunit gamma result in local cytoplasmic Jak3 being recruited to the cytoplasmic tails of the receptor. The tail becomes phosphorylated creating STAT protein binding sites. The STAT complex then also becomes phosphorylated to form a homo/heterodimer and translocate to the nucleus to bind to DNA to activate transcription. For example, interleukin IL2 binds type I receptor ILR2 resulting in Jak1 with Jak3 recruitment to the cytoplasmic gamma subunit. This interaction leads to tyrosine phosphorylation of the receptor for Stat5A with Stat5B docking. These STATs are then phosphorylated and activated by Jak1 and Jak3 leading to their dimerization and translocation for activation of specific gene transcription.

 Jak3 also has vital roles in immune cell signalling pathways; IL2 binds IL2R on T cells and natural killer cells. It has been found that in these immune cells Jak3 is critical to facilitate tyrosine phosphorylation of the cytoplasmic IL2R subunit. Throughout T cell differentiation Jak3 is required for IL7 induced activation of IL7R to activate PI3k and STATs. Ablation of Jak3 completely halted T cell proliferation.  JAK3-deficient models have phenotypes like human severe combined immunodeficiency (SCID), due to the lack of developed lymphocytes. This was linked to the interaction found between Jak3 and the T cell protein tyrosine phosphatases (TCPTP) key to cytokine signalling in haematopoietic cells.