Phosphoinositide Signaling Pathways: Study with Video Lessons, Practice Problems & Examples

The phosphoinositide signaling pathway, activated by G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs), plays a crucial role in cellular functions. GPCRs activate Gq proteins, leading to phospholipase C activation, which produces inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium signaling, essential for processes like muscle contraction and nerve cell secretion. RTKs also activate phospholipase C, recruiting PI3 kinase, which initiates signaling cascades that promote cell division and survival through Akt activation. Understanding these pathways is vital for grasping cellular communication and function.

PI Pathway

Hi. In this video, we're going to be talking about phosphoinositide or phosphoinositol signaling pathways. So this pathway is confusing in the textbook because there seems to be all these different results that happen from them, but it's not very clear on why they're happening or what's activating it, or how all these different things are being activated. So I've tried to divide this into 2 groups, and this is because the phosphoinositide signaling pathway may also be seen as the inositol phospholipid pathway, same thing. Both of these can be activated by the G protein-coupled receptors or the receptor tyrosine kinase, so the enzyme-coupled receptors. So there are 2 main pathways, and they each activate this pathway for different functions. So let's first focus on the GPCR. So how the GPCR is activated is they activate, so once they are activated, the receptors activate this G protein called Gq, and this goes on to activate phospholipase C. Now, phospholipase C is important because when cleavage happens, it results in 2 products. The first is going to be called IP₃, and the second is DAG. And if you're interested in what their names, they're listed right there. So IP₃ goes on to cause calcium signaling in the cytoplasm, And DAG goes on to activate this protein called protein kinase C, which then goes on to activate a lot of other proteins when calcium is present. So they interact. So the IP₃ brings calcium into the cell, and DAG activates proteins that are responsive to calcium. Does all make sense? And so the calcium surge in the cytoplasm triggers a lot of different events, things like egg development, muscle contraction, nerve cell secretion. So calcium is a big signaling molecule, and so this is one of these pathways that the inositol phospholipid pathway leads to the signaling of calcium. So here we have the example. So here, you've probably seen this picture before, but just want to show it to you again. So here you have this lipid, phospholipase C comes in and cleaves it. It forms DAG and IP₃. IP₃ travels down here and releases calcium, and DAG activates different proteins that are responsive to calcium to then go on and do a lot of different signaling things. Now, on the other hand, RTKs and other types of receptors like cytokine receptors will also activate phospholipase C for a different purpose. But this is still a very similar pathway. So phospholipase C, in this case, will recruit this PI 3-kinase to the membrane, PI 3 kinases. And then once this kinase is here, it can do a lot of things. So, first, it's a kinase, so it's going to add phosphates onto something, and so in this case it's going to add it onto a phosphoinositide lipid. So this is the same lipid that we talked about before. And, once this is phosphorylated, it leads to a bunch of signaling cascades, which can trigger cell division and prevent cell death. It also activates this protein called AKT, which activates a variety of other proteins. And PTEN phosphatase, remember, phosphatases are going to remove phosphates. So, this is how this is actually inactivated, is this PTEN phosphatase. So what this looks like is you have some type of receptor tyrosine kinase. You then get PI 3-kinase activation. You can get AKT activation, which is going to activate a lot of different things. And you can see that there's a ton of different other things that happen down here. You don't need to know these names. But just know these are signaling cascades. They're activating a lot of things. So that's how the RTKs activate the phosphoinositide signaling pathways. So with that, let's move on.

The inositol signaling pathway can be activated by both GPCRs and RTKs.

• A. True
• B. False

Which of the following molecules removes phosphates from PI-3 kinase?

• A. Phospholipase C
• B. Phosphatidylinositol-3 kinase
• C. PTEN Phosphatase
• D. Protein Kinase C

Here’s what students ask on this topic:

What is the role of phosphoinositide signaling pathways in cellular functions?

Phosphoinositide signaling pathways are crucial for various cellular functions. Activated by G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs), these pathways regulate processes like muscle contraction, nerve cell secretion, cell division, and survival. GPCRs activate Gq proteins, leading to phospholipase C activation, which produces inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium signaling, essential for muscle contraction and nerve cell secretion. RTKs activate phospholipase C, recruiting PI3 kinase, which initiates signaling cascades promoting cell division and survival through Akt activation. Understanding these pathways is vital for grasping cellular communication and function.

How do G protein-coupled receptors (GPCRs) activate phosphoinositide signaling pathways?

G protein-coupled receptors (GPCRs) activate phosphoinositide signaling pathways by first activating Gq proteins. Once activated, Gq proteins stimulate phospholipase C, which then cleaves a specific phospholipid to produce inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 travels to the endoplasmic reticulum, causing the release of calcium ions into the cytoplasm. This calcium surge triggers various cellular events, such as muscle contraction and nerve cell secretion. Meanwhile, DAG remains in the membrane and activates protein kinase C (PKC), which, in the presence of calcium, goes on to activate other proteins involved in diverse signaling processes.

What are the main products of phospholipase C activation in the phosphoinositide signaling pathway?

The main products of phospholipase C activation in the phosphoinositide signaling pathway are inositol trisphosphate (IP3) and diacylglycerol (DAG). When phospholipase C cleaves a specific phospholipid, it generates these two molecules. IP3 is responsible for triggering calcium release from the endoplasmic reticulum into the cytoplasm, which is crucial for various cellular processes like muscle contraction and nerve cell secretion. DAG, on the other hand, remains in the cell membrane and activates protein kinase C (PKC), which, in the presence of calcium, goes on to activate other proteins involved in multiple signaling pathways.

How do receptor tyrosine kinases (RTKs) activate phosphoinositide signaling pathways?

Receptor tyrosine kinases (RTKs) activate phosphoinositide signaling pathways by first activating phospholipase C. This enzyme then recruits PI3 kinase to the membrane. PI3 kinase phosphorylates a specific phosphoinositide lipid, leading to the activation of various signaling cascades. These cascades promote cell division and survival by activating proteins such as Akt. Akt, in turn, activates a variety of other proteins that contribute to these cellular processes. The pathway is tightly regulated, with phosphatases like PTEN deactivating the signaling by removing phosphates from the lipids.

What is the function of inositol trisphosphate (IP3) in the phosphoinositide signaling pathway?

Inositol trisphosphate (IP3) plays a critical role in the phosphoinositide signaling pathway by triggering the release of calcium ions from the endoplasmic reticulum into the cytoplasm. This calcium release is essential for various cellular processes, including muscle contraction, nerve cell secretion, and egg development. IP3 is produced when phospholipase C cleaves a specific phospholipid. Once formed, IP3 binds to its receptors on the endoplasmic reticulum, causing the release of stored calcium ions, which then participate in various signaling events within the cell.