Mouse Lymphocyte Adaptor Protein (Lnk) Protein

Background

SH2B3, also known as LNK, is an SH2 domain-containing adaptor protein that acts as a negative regulator of cytokine and growth factor receptor signaling. It interacts with signaling molecules downstream of receptors like JAK2, MPL, and KIT, modulating pathways such as JAK/STAT and PI3K/Akt to maintain signaling balance. SH2B3 is predominantly expressed in hematopoietic cells, where it regulates hematopoiesis, immune cell development, and inflammatory responses by suppressing excessive cytokine signaling. Mutations or loss of SH2B3 are associated with hematological disorders, including myeloproliferative neoplasms, leukemia, and autoimmune diseases, due to hyperactive cytokine signaling. SH2B3 also plays roles in cardiovascular diseases and metabolic regulation by controlling inflammatory signaling and cellular proliferation. Knockout studies show hyperproliferation of hematopoietic cells, increased inflammatory responses, and susceptibility to myeloproliferative disorders, emphasizing its role as a critical negative regulator of hematopoietic and immune cell signaling.