EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion.

A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that control GBM cell dissemination is critical for developing effective therapies to treat GBM.

MLK3 Signaling in Cancer Invasion.

Mixed-lineage kinase 3 (MLK3) was first cloned in 1994; however, only in the past decade has MLK3 become recognized as a player in oncogenic signaling. MLK3 is a mitogen-activated protein kinase kinase kinase (MAP3K) that mediates signals from several cell surface receptors including receptor tyrosine kinases (RTKs), chemokine receptors, and cytokine receptors. Once activated, MLK3 transduces signals to multiple downstream pathways, primarily to c-Jun terminal kinase (JNK) MAPK, as well as to extracellular-signal-regulated kinase (ERK) MAPK, P38 MAPK, and NF-κB, resulting in both transcriptional and post-translational regulation of multiple effector proteins.

Protein interaction module-assisted function X (PIMAX) approach to producing challenging proteins including hyperphosphorylated tau and active CDK5/p25 kinase complex.

Many biomedically critical proteins are underrepresented in proteomics and biochemical studies because of the difficulty of their production in Escherichia coli. These proteins might possess posttranslational modifications vital to their functions, tend to misfold and be partitioned into bacterial inclusion bodies, or act only in a stoichiometric dimeric complex. Successful production of these proteins requires efficient interaction between these proteins and a specific "facilitator," such as a protein-modifying enzyme, a molecular chaperone, or a natural physical partner within the dimeric complex.