Signaling by LTK

LTK is activated by the binding of cytokines ALKAL1 and ALKAL2 to the ECD. Ligand binding induces trans-autophosphorylation in the intracellular domain of the receptor and promotes the interaction and activation of downstream signaling molecules such as SHC, IRS1, CBL and PI3K with the phosphorylated receptor. Note however that much of the early functional studies on LTK were conducted before the identification of ALKAL1 and 2 as physiological ligands. In consequence, many of these studies were carried out using chimeric receptors consisting of the ECD (and stimulating ligands) of well-characterized receptors fused to the intracellular domain of LTK.

The exact role of LTK signaling is likewise not fully elucidated. Expression of the chimeric LTK proteins described above promotes neurite outgrowth and cell survival. A role for LTK in the regulation of transport from the ER to the Golgi has also been proposed, and one study suggests that LTK may actually bean ER-resident protein. More recently, fusions of LTK have been identified in non-small cell lung cancer.