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Biology: Cell-Cycle Regulation: Protein Kinases


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About this Lesson

  • Type: Video Tutorial
  • Length: 10:39
  • Media: Video/mp4
  • Use: Watch Online & Download
  • Access Period: Unrestricted
  • Download: MP4 (iPod compatible)
  • Size: 115 MB
  • Posted: 07/01/2009

This lesson is part of the following series:

Biology Course (390 lessons, $198.00)
Biology: Cell Reproduction - Mitosis and Meiosis (16 lessons, $23.76)
Biology: Regulating Mitosis (4 lessons, $7.92)

Taught by Professor George Wolfe, this lesson was selected from a broader, comprehensive course, Biology. This course and others are available from Thinkwell, Inc. The full course can be found at http://www.thinkwell.com/student/product/biology. The full course covers evolution, ecology, inorganic and organic chemistry, cell biology, respiration, molecular genetics, photosynthesis, biotechnology, cell reproduction, Mendelian genetics and mutation, population genetics and mutation, animal systems and homeostasis, evolution of life on earth, and plant systems and homeostasis.

George Wolfe brings 30+ years of teaching and curriculum writing experience to Thinkwell Biology. His teaching career started in Zaire, Africa where he taught Biology, Chemistry, Political Economics, and Physical Education in the Peace Corps. Since then, he's taught in the Western NY region, spending the last 20 years in the Rochester City School District where he is the Director of the Loudoun Academy of Science. Besides his teaching career, Mr. Wolfe has also been an Emmy-winning television host, fielding live questions for the PBS/WXXI production of Homework Hotline as well as writing and performing in "Football Physics" segments for the Buffalo Bills and the Discover Channel. His contributions to education have been extensive, serving on multiple advisory boards including the Cornell Institute of Physics Teachers, the Cornell Institute of Biology Teachers and the Harvard-Smithsonian Center for Astrophysics SportSmarts curriculum project. He has authored several publications including "The Nasonia Project", a lab series built around the genetics and behaviors of a parasitic wasp. He has received numerous awards throughout his teaching career including the NSTA Presidential Excellence Award, The National Association of Biology Teachers Outstanding Biology Teacher Award for New York State, The Shell Award for Outstanding Science Educator, and was recently inducted in the National Teaching Hall of Fame.

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You can well imagine that the cell cycle and the regulation of the cell cycle is unbelievably complex and crucial to the survival of the organism. Let's just think about this. When do you turn off mitosis? How does a cell know to go from G to S1 to G2? How do these things occur? Well, here's the thing. We're still figuring it out. We're still not absolutely positive. But you know what? We've found things called checkpoints, and that's what I want to tell you about today: little places called checkpoints where it looks like we can stop a certain thing and move to another one, et cetera.
Let me just give you an example. Let's go back to that diagram of the cell cycle. So you remember it went something like this. We'll make it a circle. And remember that G1 was a big old part of the cell cycle, and that from G1 we went into S, and from S we went into G2. And then over here we had mitosis and cytokinesis. What I want to show you--here's the analogy I want to use. Imagine--have you ever done laundry? I know some of you haven't, but if you've ever done laundry and you know the washing machine, and you've got that dial on the washing machine. Picture that dial, that whole thing, as the cell cycle. And you know that there are checkpoints on there, and you could take it out and turn it or stop it, and it will progress to a certain point.
Well, we're going to imagine that this is the washing machine and we have places where we can do checks, and we call these after where they are. For example, right here is a G1 checkpoint. We also apparently have a G2 checkpoint, and we even have an M checkpoint right here. And so if you imagine that washing machine dial sitting right there and progressing through in that direction as it's going tick-tick-tick, there are going to be some situations where it's going to stop at G2 and not move into M. There are going to be some situations where it's going to stop at G1 and not move on. I'll give you a good example of that one. Let's think of a cell that's rapidly dividing, like a cell of an embryo. That cell of the embryo may not leave G1 for quite a while. I don't mean a cell of an embryo. Like a nerve cell--that's an even better one. Embryos we'll talk about down here.
A nerve cell, which might stop replicating--why? Well, let's take your brain. Once your skull forms, you don't want to be building up a whole lot more of brain material. Now we're finding out more and more that the brain is a dynamically recycling cell situation where some cells are broken down and some new ones are made, but there comes a time when you want your brain to stop growing because of your skull. You're going to want to stop the cell cycle at G1 and actually keep those cells in something called G-zero, which is "We don't want you guys dividing anymore." So some cells just stop dividing. Some cells don't divide until there is some kind of damage and then they can somehow get through the G1 checkpoint and move on, do some synthesis and do some mitosis. Other cells, you may want to stop them after synthesis, and so they're growing and growing and growing, but you may not want the chromosomal events to begin. It's a complex story with some answers. We really do have some answers as to how we control the cell cycle. Let's talk about some of those answers.
The first thing I want to talk about is a group of proteins called protein kinases. This is going to be our first example of the way a cell regulates the cell cycle. What are protein kinases? Protein kinases are enzymes. They're enzymes that add ATP. You've seen kinases in respiration. So generally speaking, these are going to phosphorylate--phosphate groups. They're going to add phosphate groups, usually from ATP, but GTP, whatever. So they're going to add phosphate groups. It turns out that protein kinases are usually inactive. The protein kinases that regulate the cell cycle are usually inactive unless an activator protein is present, and that activator protein is called cyclin. So a protein kinase plus cyclin yields an active protein kinase.
Let's make that even still more concrete. Let me give you some examples. In the case of one--we're going to call one of these CDKs. CDK is one of these protein kinases and it stands for "cyclin dependent kinases." Cyclin dependent kinases, CDK. And here's the story with CDK. CDK is kind of like a molecule; I'm going to draw it like this. And it's inactive unless a molecule of cyclin comes along, which might look something like this. And when cyclin fits into here, this will activate it. And we call that activated form of the CDK--this is alphabet soup, guys, and I'm sorry--MPF. So what is MPF? MPF is this complex. MPF stands for "maturation promoting factor." Maturation promoting factor, MPF. Why is this important? I want you to understand why we call it MPF. It's going to promote maturation. What's maturation? Growth. So what do we have? We have CDK plus cyclin yields MPF.
Let me give you one example of how a protein kinase might regulate the cell cycle, and the one I want to use is the G2 checkpoint. So we're going to go to that G2 checkpoint. Now, the G2 checkpoint is kind of interesting, and I want to show you this graph first. Let's take a look at the red line. Now the peaks here are happening during mitosis, so chromosomal movement is happening there. And I want you to see the red line which is--well, look at that! That is the concentration of cyclin. So it just seems that as cyclin gets high right around G2, only when cyclin is at a certain level can we move into mitosis. And therefore the whole idea of concentration of cyclin seems to be important.
So what happens? Well, here we go. Cyclins are accumulating through G1. Cyclins are accumulating through S. Cyclins are accumulating through G2. All right, what are they doing while they're accumulating? They're associating. What are they associating with? They're associating with CDK. So the cyclins accumulate, accumulate, accumulate--look, we're at G2--accumulate, accumulate. The more they accumulate, the more of this MPF you form. Now once we are here at this maturation promoting factor, we now can get an active phosphorylation. So what does the MPF do? The MPF does a phosphorylation. When it phosphorylates, it turns out that that phosphorylation, one of the places it phosphorylates is a structure you know about, called the nuclear lamina. What is the nuclear lamina? It's the inside of the nuclear envelope that holds the nucleus together. And when you phosphorylate the nuclear lamina, guess what happens? It breaks down.
Now, think back to mitosis. What was the first thing that started to happen in the prophase, the prometaphase? The nuclear membrane broke down. Why? Well, put it all together. Cyclin up; MPF form. MPF forms; nuclear membrane can break down. Nuclear membrane can break down; spindle fibers can get through. Spindle fibers can get through; they can attach to chromosomes. Chromosomes can split. This is a real control mechanism.
One last thought. How does cyclin go away? Why don't you just keep breaking down your nuclei? Did you ever hear of proteosomes? Well, golly, gee whiz. In essence, cyclin is going to turn itself off. Because one of the things we find out is that another thing MPF does is it triggers the breakdown of cyclin. And what's going to happen when cyclin breaks down? So MPF, besides doing that lamina thing and causing that breakdown, will also trigger digestion of cyclins, which therefore is going to end up inactivated--inactive protein kinases or inactive MPF.
It sounds like a complicated story, and it is. And there is still a lot more to talk about. That was a G2 checkpoint. There are some other checkpoints, too, one that happens in M.
Cell Reproduction
Regulating Mitosis
Cell Cycle Regulation: Protein Kinases Page [1 of 2]

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