Large tumor suppressor 2, LATS2, activates JNK in a kinase-independent mechanism through ASK1.

Apoptosis signal-regulating kinase 1 (ASK1) is an important mediator of the cell stress response pathways. Because of its central role in regulating cell death, the activity of ASK1 is tightly regulated by protein-protein interactions and post-translational modifications. Deregulation of ASK1 activity has been linked to human diseases, such as neurological disorders and cancer.

The OncoPPi Portal: an integrative resource to explore and prioritize protein-protein interactions for cancer target discovery.

Motivation: As cancer genomics initiatives move toward comprehensive identification of genetic alterations in cancer, attention is now turning to understanding how interactions among these genes lead to the acquisition of tumor hallmarks. Emerging pharmacological and clinical data suggest a highly promising role of cancer-specific protein-protein interactions (PPIs) as druggable cancer targets. However, large-scale experimental identification of cancer-related PPIs remains challenging, and currently available resources to explore oncogenic PPI networks are limited.

Regulation of ASK1 signaling by scaffold and adaptor proteins.

The mitogen-activated protein kinase (MAPK) signaling pathway is a three-tiered kinase cascade where mitogen-activated protein kinase kinase kinases (MAP3Ks) lead to the activation of mitogen-activated protein kinase kinases (MAP2K), and ultimately MAPK proteins. MAPK signaling can promote a diverse set of biological outcomes, ranging from cell death to proliferation. There are multiple mechanisms which govern MAPK output, such as the duration and strength of the signal, cellular localization to upstream and downstream binding partners, pathway crosstalk and the binding to scaffold and adaptor molecules.

The OncoPPi network of cancer-focused protein-protein interactions to inform biological insights and therapeutic strategies.

As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes.

The pseudophosphatase MK-STYX induces neurite-like outgrowths in PC12 cells.

The rat pheochromocytoma PC12 cell line is a widely used system to study neuronal differentiation for which sustained activation of the extracellular signaling related kinase (ERK) pathway is required. Here, we investigate the function of MK-STYX [MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein] in neuronal differentiation. MK-STYX is a member of the MAPK phosphatase (MKP) family, which is generally responsible for dephosphorylating the ERKs.