Functional Analysis of MKNK2 Isoforms in response to MAPK phosphorylation
Primary Investigator (PI) Name
Carol Chrestensen
Department
CSM – Chemistry and Biochemistry
Abstract
MKNK2 is a serine/threonine kinase activated downstream of the mitogen-activated protein kinases (MAPK) pathway. p38 and ERK1/2 are known kinase activators of MKNK2, though MKNK2 is known to preferentially interact with ERK1/2. MKNK2 belongs to the MKNK family, which includes two genes, MKNK1 and MKNK2. These kinases phosphorylate the eukaryotic initiation factor eIF4E, which is a regulator of mRNA translation, cell growth, and oncogenic signaling. In recent years, MKNK2 has been studied for its role in cancer, where phosphorylation of eIF4E promotes tumorigenesis. MKNK2 is alternatively spliced into two isoforms, MKNK2-long and MKNK2-short. The long form has been reported to act as a tumor suppressor, while the short form functions as an oncogene. In this project, we purified GST-versions of both MKNK2 proteins and performed a kinase assay to test the ability of both isoforms to be a substrate of ERK or p38 MAP kinase, and if the short and long isoforms can phosphorylate kemptide after activation. The information from these experiments could help with the development of targeted inhibitors of oncogenic pathways.
Disciplines
Biochemistry
Functional Analysis of MKNK2 Isoforms in response to MAPK phosphorylation
MKNK2 is a serine/threonine kinase activated downstream of the mitogen-activated protein kinases (MAPK) pathway. p38 and ERK1/2 are known kinase activators of MKNK2, though MKNK2 is known to preferentially interact with ERK1/2. MKNK2 belongs to the MKNK family, which includes two genes, MKNK1 and MKNK2. These kinases phosphorylate the eukaryotic initiation factor eIF4E, which is a regulator of mRNA translation, cell growth, and oncogenic signaling. In recent years, MKNK2 has been studied for its role in cancer, where phosphorylation of eIF4E promotes tumorigenesis. MKNK2 is alternatively spliced into two isoforms, MKNK2-long and MKNK2-short. The long form has been reported to act as a tumor suppressor, while the short form functions as an oncogene. In this project, we purified GST-versions of both MKNK2 proteins and performed a kinase assay to test the ability of both isoforms to be a substrate of ERK or p38 MAP kinase, and if the short and long isoforms can phosphorylate kemptide after activation. The information from these experiments could help with the development of targeted inhibitors of oncogenic pathways.