The c-Jun N-terminal kinase (JNK) family is a group of regulatory kinases with important functions in cell morphogenesis, inflammation, differentiation, and cell death (1). Aberrant activation of JNK family proteins in cancers has led to interest in small molecule JNK inhibitors as a therapeutic strategy (1). JNK1, also known as MAPK8, is expressed in most tissues and is involved in transduction of extracellular signals such as growth factors or cytokines though a phosphorylation cascade to elicit diverse intracellular responses (1). JNK phosphorylation substrates include p53, AP-1, c-Myc, and Bcl-2 (1). Defects in JNK signaling have been observed in inflammatory and neurodegenerative disorders (1). For example, increased JNK1 activity leads to hyperphosphorylation of tau in Alzheimer’s disease (2). A recent study reduced JNK1 activity by using heterozygous JNK1 deficient mice and examined the effect on β-amyloid plaque number and inflammatory markers (3). While immunohistochemistry with JNK1 antibodies confirmed reductions in protein levels, this was not sufficient to prevent the development of neuropathologies (3). This research suggests disruption of multiple JNK family proteins may be needed for therapeutic efficacy. In addition to these disorders, a number of small molecule JNK1 inhibitors are currently in development to block carcinogenesis (4). One of these JNK1 inhibitors can covalently bind and irreversibly inhibit the phosphorylation of c-Jun by JNK1 (5). Through western blotting with the JNK1 antibody, the researchers were able to examine the binding kinetics of their drug to assess working concentrations (5). Another potential anti-cancer drug, sulindac has been shown to target JNK1 signaling and is effective at treating colorectal cancer (6). In a separate study sulindac’s activity against prostate cancer cells was demonstrated by Du et al. (6). This study used a JNK1 antibody to examine phosphorylation and activation of JNK1 following drug treatment and confirmed its role prostate cancer proliferation (6). Similarly, the activation of JNK1 in pancreatic cancer cells following drug treatment was assessed using phospho-specific JNK1 antibodies and was shown to be important for the induction of autophagy (7). Together these studies demonstrate some of the important research applications of JNK1 antibodies in drug development and cell biology.
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Novus Biologicals offers JNK1 reagents for your research needs including:
