Question

does Nerve Growth Factor (NGF) treatment of PC12 cells increase in MAPK phosphorylation or increase in MAPK protein? Or does it increase both?

Answer 1

Nerve growth factor (NGF) is a neurotrophins which mechanisms of action has been extensively studied in rat pheochromocytoma cell line PC12. When PC12 cells are exposed to NGF, cells exit the cell cycle and gradually differentiate into sympathetic neuron like cells. NGF binds to TrkA tyrosine kinase leading to ligand binding and receptor dimerization that leads to the activation of small guanine nucleotide binding protein Ras. This step is followed by sequential activation and phosphorylation of Raf, mitogen activated protein kinase (MAPK) or extracellular signal regulated kinase (ERK). ERKs is a subgroup of pp90 ribosomal S6 kinases (RSKs) and MAPK superfamily. One of the important function of ERKs is to induce the phosphorylation and activation of transcription factor. These functions leads to the initiation of new programs of gene expression in the nucleus of PC12 cells. Multiple research articles have clearly shown the the induction of a class of genes termed as immediate early gene (IEGs) when PC12 cells are treated with NGF. NGF was also found to activate p38 MAPK and its downstream effector MAPKAP kinase 2. p38 acts as a signal transduction mediator and have shown its role in inflamation, cell death, cell cycle, cell development and differentiation as wellas tumorigenesis and senescence in specific type of cells.