LMTK3

Description

The LMTK3 (lemur tyrosine kinase 3) is a protein-coding gene located on chromosome 19.

LMTK3 is a protein encoded by the LMTK3 gene in humans. It is often overexpressed in human cancers, where it promotes tumor growth, invasion, metastasis, and therapy resistance. LMTK3 was first identified in 2011 as a regulator of ERα, promoting its upregulation by inhibiting PKC and preventing its degradation through direct phosphorylation. Research has linked LMTK3 to cancer in various types, including glioblastoma, non-small cell lung cancer, thyroid malignancies, and bladder cancer. A small molecule inhibitor, C28, has been developed for LMTK3 and demonstrates potent anti-cancer activity in vitro and in vivo. The most well-characterized physiological role of LMTK3 is in the central nervous system. It is expressed in the cerebral cortex, striatum, cerebellum, hippocampus, olfactory bulb, and tubercle. LMTK3 knockout mice exhibit increased hyperactivity and reduced anxiety compared to wild-type counterparts. These mice also display lower levels of depression-like behavior in forced swim and tail suspension tests.

LMTK3 is a protein kinase that directly phosphorylates ESR1 (in vitro), protecting it from degradation by the proteasome. LMTK3 also indirectly regulates ESR1 levels through the PKC-AKT-FOXO3 pathway. It inhibits PKC activity and AKT phosphorylation, leading to increased binding of the FOXO3 transcriptional activator to the ESR1 promoter and enhanced ESR1 transcription. Additionally, LMTK3 is involved in the endocytic trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons.

LMTK3 is also known as AATYK3, LMR3, PPP1R101, TYKLM3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing