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Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis.

Marusiak, Anna A Stephenson, Natalie L Baik, Hayeon Trotter, Eleanor W Li, Yaoyong Blyth, Karen Mason, Susan Chapman, Phil Puto, Lorena A Read, Jon A ...

Published in Cancer research

MLK4 is a member of the mixed-lineage family of kinases that regulate the JNK, p38, and ERK kinase signaling pathways. MLK4 mutations have been identified in various human cancers, including frequently in colorectal cancer, where their function and pathobiological importance have been uncertain. In this study, we assessed the functional consequence...

TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signa...

Copp, Jeremy Manning, Gerard Hunter, Tony

Published in Cancer research

The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic component of two evolutionarily conserved signaling complexes. mTOR signaling complex 1 (mTORC1) is a key regulator of growth factor and nutrient signaling. S6 kinase is the best-characterized downstream effector of mTORC1. mTOR signaling complex 2 (mTORC2) has a role...

Cancer-associated loss-of-function mutations implicate DAPK3 as a tumor-suppressing kinase.

Brognard, John Zhang, You-Wei Puto, Lorena A Hunter, Tony

Published in Cancer research

Cancer kinome sequencing studies have identified several protein kinases predicted to possess driver (i.e., causal) mutations. Using bioinformatic applications, we have pinpointed DAPK3 (ZIPK) as a novel cancer-associated kinase with functional mutations. Evaluation of nonsynonymous point mutations, discovered in DAPK3 in various tumors (T112M, D16...

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