Write a note on calcium signaling.
Answers
Process and Regulation of Calcium Signaling Pathway
G protein-coupled receptor (GPCR) activates phospholipase C β (PLC β) and RTK activates PLC γ cleave phosphatidylinositol 4, 5 bisphosphate (PIP2) into 1, 4, 5-inositol trisphosphate (IP3) and diacylglycerol (DAG). Ca2+ binds to the C2 domain of PKCα, β1, β2, and γ subtypes initiate translocation to the membrane, where coincident DAG binding activates Protein kinase C (PKC). Ca2+-sensitive DAG kinase phosphorylates DAG to produce phosphatidic acid, while DAG lipase converts DAG to arachidonic acid, thus to generate a host of bioactive molecules.
Ca2+ can be directly released into the nucleoplasm via IP3 receptor (IP3R) and ryanodine receptor (RYR). The Ca2+ -sensitive protein phosphatase calcineurin (CaN) activates the transcription factor NFAT, which plays a critical role in Ca2+ signaling pathway process. Several different transcription factors and their upstream kinases are regulated by calcium. However, transcription is often not directly controlled by calcium ions but requires the involvement of specific signaling molecules and adaptors, which are activated by calcium inside or outside the nucleus. Thus, several routes exist by which calcium can relay a message to the nuclear transcription machinery. For example, the presence of nuclear calcium has been demonstrated as a requirement for the induction of activity-dependent, cAMP response element binding protein (CREB)-mediated gene transcription. One of the most widely occupied routes is the calcium-mediated activation of protein kinase cascades in the cytoplasm such as forming Calmodulin (CALM) to CaMKII and CaMKIV and their subsequent translocation into the nucleus.
The ERK1/2-MAPK cascade is a major target of synaptically evoked calcium signals, during which Ras and PKC are required to yield physiologically relevant activity of ERK1/2 through activating Raf and MEK1/2. PKC regulates CARMA1-Bcl 10- Malt1 signalosome to activate IKK, which releases transcription factor (p50/p65) from IKB. ERK1, p50 and p65 play an important role in gene expression and control the activity of many different intracellular signaling substrates in the nucleus.
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