Mitogen-activated protein kinases (MAPKs) are important signaling proteins needed to transmit and relay extracellular stimuli and to illicit intracellular responses (1). The MAPK family of proteins are serine/threonine kinases that are able to phosphorylate and activate downstream kinases in a signal cascade that regulates diverse cell responses such as gene expression, metabolism, apoptosis, and differentiation (1). Notable members of the MAPK family include ERK, JNK, and p38 (1). Misregulation of these pathways has been implicated in neurodegenerative diseases as well tumorigenesis (1). ERK1, also known as MAPK3, is one of the downstream kinases activated by receptor-tyrosine kinases such as EGFR and the Ras GTPase (2). ERK1/2 can phosphorylate hundreds of substrate proteins including transcription factors and cytoplasmic regulators (2). Additionally, increased activity of the ERK1/2 cascade is observed in about a third of all human cancers (2). Inhibiting components of this pathway, such as B-Raf, is one anti-tumor therapeutic strategy being employed. Currently inhibitors targeting mutated B-Raf are in development and have proven effective in the treatment of melanoma (2).
The ability to measure ERK1 activation using phospho-specific ERK1 antibodies provides a valuable tool in cancer research. For example, a recent study used phospho-specific ERK1 antibodies for western blotting assay to show the effectiveness of various drugs on ERK1/2 inhibition (3). They identified norathyriol, a metabolite of a natural product found in mangos, as an effective suppressor of UV-induced skin cancer (3). Using a similar approach researchers from Johns Hopkins University used ERK1 antibodies to compare the levels of total ERK1 and phospo-ERK1 (4). Their study demonstrated pyruvate kinase M2 (PKM2) is able to induce ERK1 activation and facilitate proliferative signaling in cancer cells (4). Apart from roles in tumorigenesis, ERK1 has been studied extensively for its role in development and cell differentiation. Using ERK1 conditional knockout mice and monitoring proteins levels with ERK1 antibodies, researchers from Case Western Reserve University showed lineage specification and differentiation of osteoblasts depends on ERK1 activity (5). ERK1 also contributes to early embryonic development as shown by by Krens et al. (6). ERK1 levels in knockdown zebrafish embryos were assessed through immunostaining with ERK1 antibodies and changes in gene expression were monitored (6). Their study revealed essential roles for ERK1 in dorsal-ventral patterning and cell migration (6). These diverse findings demonstrate the variety of applications for ERK1 antibodies in researching development and disease.
Novus Biologicals offers ERK1 reagents for your research needs including: