Big Mitogen-activated Protein Kinase 1 (BMK1) Is a Redox-sensitive Kinase

Abstract

Mitogen-activated protein (MAP) kinases are a multigene family activated by many extracellular stimuli. There are three groups of MAP kinases based on their dual phosphorylation motifs, TEY, TPY, and TGY, which are termed extracellular signal-regulated protein kinases (ERK1/2), c-Jun N-terminal kinases, and p38, respectively. A new MAP kinase family member termed Big MAP kinase 1 (BMK1) or ERK5 was recently cloned. BMK1 has a TEY sequence similar to ERK1/2 but has unique COOH-terminal and loop-12 domains. To define BMK1 regulation, its activation in cultured rat vascular smooth muscle cells was characterized. Angiotensin II, phorbol ester, platelet-derived growth factor, and tumor necrosis factor-␣ were the strongest stimuli for ERK1/2 but were weak activators of BMK1. In contrast, H 2 O 2 caused concentration-dependent activation of BMK1 but not ERK1/2. Sorbitol activated both BMK1 and ERK1/2. BMK1 activation by H 2 O 2 was calcium-dependent and appeared ubiquitous as shown by stimulation in human skin fibroblasts, human vascular smooth muscle cells, and human umbilical vein endothelial cells. These findings demonstrate that activation of BMK1 is different from ERK1/2 and suggest an important role for BMK1 as a redox-sensitive kinase.

Kinase domain mutants of Bcr enhance Bcr-Abl oncogenic effects

“…For western blot analysis of Bcr-Abl and Bcr, total proteins were isolated as described (Abe et al, 1996). Blots were probed with either anti-HA (Invitrogen, Carlsbad, CA, USA), antiBcr (1-16) or anti-Abl 8E9 monoclonal antibody (Guo et al, 1994).…”

Signaling by dual specificity kinases

“…It has been recently observed that the osmotic-and oxidative-stress can activate ERK5 (Abe et al, 1996). Analysis of the signaling mechanism indicates that MKK5-ERK5 activation results in the phosphorylation of MEF2C, the transcription factors belonging to the myocyte enhancer factor-2 (MEF2)-family (Kato et al, 1997).…”

The oncogenic TEL/PDGFRβ fusion protein induces cell death through JNK/SAPK pathway

“…Four groups of MAPKs have been identi®ed in mammalian cells; the extracellular signalregulated kinases (ERKs) (also referred to as p42/44 MAPK) (for review see Davis, 1993), the c-Jun Nterminal kinases/stress-activated protein kinases (JNK/ SAPKs) (De rijard et al, 1994;Kallunki et al, 1994;Kyriakis et al, 1994), p38/CSBP/RK/MPK2/MX12 (Han et al, 1994;Lee et al, 1995), and ERK5 (Lee et al, 1997., Abe et al, 1996. The mammalian ERKs are involved in growth factor-mediated activation and di erentiation of a variety of cells, and are activated by growth factors and mitogens such as epidermal growth factor (EGF), PDGF and insulin.…”