Following LR activation, the associated JAK2 kinase is activated, auto-phosphorylates, and trans-phosphorylates the LR. This creates binding sites for SH2 domain-containing proteins, which activate downstream signaling. JAK2 phosphorylates RPTPe, which deactivates JAK2 (dashed arrows). Also shown are PTP1B that targets JAK2, and TC-PTP that targets STAT3.