Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms

TLDR

Mammalian MAP kinases, including ERK, JNK, and p38, are activated by dual phosphorylation on threonine and tyrosine residues. The authors cloned two human MAP kinase kinases, MKK3 and MKK4, which phosphorylate and activate p38 MAP kinase. MKK3 and MKK4 activate p38, MKK4 also activates JNK, and none activate ERK, demonstrating that distinct MAP kinase pathways are defined by specific MAP kinase kinases.

Abstract

Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.