Comparison between the AMR and IL-6R signaling pathways leading to TPO mRNA expression. Binding of desialylated platelets to the hepatic AMR composed of one ASGPR2 and two ASGPR1 subunits activates JAK2. IL-6 binding to its hepatic receptor composed of one gp80 and two gp130 subunits activates gp130-associated JAK1, and to a lesser extent JAK2. Both JAK1 and JAK2 phosphorylate STAT3, resulting in its translocation to the nucleus where it stimulates mRNA expression of TPO and acute phase response proteins. It is unclear whether JAK2 directly associates with ASGPR1 and whether STAT3 directly binds to the TPO promoter.