Inosrtol 1,4,5-trisphosphate (IP_3) and dracylglycerol (DAG) are second messenge
ID: 67000 • Letter: I
Question
Inosrtol 1,4,5-trisphosphate (IP_3) and dracylglycerol (DAG) are second messenger molecules derived from the cleavage of the phosphntidylmositol 4 5-bisphosphate (PIP_2) by activated phospholipase C Describe the role of IP_3 in the release of Ca^2+ for the endoplasmic reticulum. How do cells replenish the endoplasmic reticulum stores of Ca^?+? What is the principle function of DAG? 8 In TGFbeta signaling pathway, R-Smads (receptor-regulated Smads) are a key component. Please describe how R-Smads go from an inactive to an active state and what do R-Smads associate with in an active state.Explanation / Answer
7.
IP3 is a soluble molecule and is capable of diffusing through the cytoplasm to the ER, or the sarcoplasmic reticulum (SR) in the case of muscle cells, once it has been produced by the action of PLC. Once at the ER, IP3 is able to bind to the Ins3P receptor (Ins3PR) on a ligand-gated Ca2+ channel that is found on the surface of the ER. The binding of IP3 (the ligand in this case) to InsP3R triggers the opening of the Ca2+ channel, and thus release of Ca2+ into the cytoplasm.
The depleted stores in the ER replenish their calcium levels via a mechansim called the store operated calcium entry. A small but highly selective calcium release activated current is generated across ER and with the help of transmembrane proteins STIM1 and Orai, the calcium reserves are replenished.
DAG remains in the inner layer of the plasma membrane. It recruits Protein Kinase C (PKC) — a calcium-dependent kinase that phosphorylates many other proteins that bring about the changes in the cell.
8.
R-SMADs are receptor-regulated SMADs. SMADs are transcription factors that transduce extracellular TGF- superfamily ligand signaling from cell membrane bound TGF- receptors into the nucleus where they activate transcription TGF- target genes. R-SMADS are directly phosphorylated on their c-terminus by type 1 TGF- receptors through their intracellular kinase domain, leading to R-SMAD activation. R-SMADs include SMAD1, SMAD2, SMAD3, SMAD5, and SMAD8. In response to signals by the TGF- superfamily of ligands these proteins associate with receptor kinases and are phosphorylated at an SSXS motif at their extreme C-terminus. These proteins then typically bind to the common mediator Smad or co-SMAD SMAD4.