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By Olga Kuchment

Interview with a protein

The domains of Sos1 have their say


[Published 11th April 2008 03:18 PM GMT]

The Sos1 protein participates in several eukaryotic cell signaling pathways, including insulin, FGF, and EGF signaling. These pathways lead to cell growth and survival, cytoskeletal organization, or changes in transcription. Mice lacking Sos1 die as embryos. A serious human genetic disorder called Noonan syndrome has recently been linked to mutations in Sos1.

My lab mates and I here at the University of California, Berkeley, study how proper Sos1 function depends on the different domains of Sos1. In a very rare journalistic opportunity, I was able to interview a few of the Sos1 domains. I wanted to learn more about their jobs.

Kuchment: Cdc25, could I ask you a few questions about your work?

Cdc25: Sure, but make it quick.

Kuchment: So what do you do in Sos1?

Cdc25: I catalyze the exchange of GDP for GTP in molecules of Ras. That way, very important signals can continue to be sent to various parts of the cell. Actually, Rem and I make a really good team, and when we have an allosteric Ras bound we really get cracking. If it wasn't for those DH and PH domains blocking that binding site all the time, we'd get so much more work done!

Kuchment: Say, is that the PXXP region over there?

Cdc25: That's right. That guy is a complete slacker. He's out there catching passing SH3 domains all day. I keep telling him to take control of his life. He's always like, 'Dude, you gotta hang loose, go with the flow.' Well, that's why you don't see him catalyzing important reactions. Anyway, I can't stand around talking all day. I need to focus on getting in shape for binding Ras.

Kuchment: DH domain, what do you do?

DH domain: Well... most of the time I'm just stuck to the side of the Rem domain, with my buddy PH. To tell you the truth, sometimes I feel like I'm missing out on life. My cousin in Dbl (I was named Dbl Homology -- DH for short -- after him) catalyzes GDP to GTP exchange... It would be so exciting if I could do that!

PH: Did somebody say lipids? I could really use a lipid head group right now, like maybe a phosphoinositol-4,5-bisphosphate, you know? I just love the way the negatively charged phosphates fit with my positively charged arginines and lysines. Hey guys, let's go hang out by the cell membrane! Any takers?

Histone: I'm up for it.

Kuchment: Histone domain, what do you do?

Histone: Well, I also like negatively charged lipid head groups. And I work pretty closely with the helical linker between the PH and Rem domains, one arginine in particular.

Kuchment: Could you be more specific?

Histone: Sorry, I'm not at liberty to say more. Those results have not been published.

Kuchment: Have you heard the news about Noonan syndrome being linked to mutations in Sos1?

Histone: Yes. Very disturbing. I am quite attached to that arginine in the helical linker. If it was mutated to glycine, it would really disrupt my work.

As you can see, there is much more to this story that is not revealed here. I will continue to strive to get the whole story on the lives of cell signaling protein domains.

Olga Kuchment is a PhD student in John Kuriyan's lab at the University of California, Berkeley. She does research in molecular biology and in her free time enjoys hanging out with family and friends, taking trips to Point Reyes, and conducting imaginary interviews with the proteins she studies.

Olga Kuchment
mail@the-scientist.com

 

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comment:
Fabulous interview
by SAKTHIKUMAR AMBADY

[Comment posted 2008-04-16 10:32:21]

Thank you Olga for the article. It was fresh new approach trying to explain a very complex biological process. This would be a fun way to teach the subject to youngsters. I liked it very much. In fact even I understand the subject better this way.




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comment:
very exciting
by anonymous poster

[Comment posted 2008-04-15 00:29:43]

Thanks Olga for introducing us a vivid approach to understand the complex biological system! Actually, I always thought, the cell is just like the society and the proteins within are like the people. So just like people in the society must conform to the rules of the society, protens within the cells should also conform to the rules the cell made. One protein has both the friends and the enemies. And once stimulated by certain cytokines, some proteins must make team with certain proteins to perform some things to response. However, after the stimulus, the proteins remain live theirs normal lives, every protein does its own business. All in all, the proteins in cell live an order life, if the order is disrupted, that is the cancer comes!




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comment:
Very Nice !
by anonymous poster

[Comment posted 2008-04-13 04:59:40]

It is so delightful to see someone take a new, fun approach to explaining a complex system. As a former educator (semi-retired) I appreciate any method that makes learning more fun and interesting, and gives me new ideas on how to present a complicated topic in a lighthearted manner. I guarantee I will remember far more about the Sos1 signaling system presented as an interview of the proteins than reading a dry academic description !!




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comment:
Very refreshing!
by anonymous poster

[Comment posted 2008-04-12 06:30:01]

I agree with John Toeppen; this was very engaging, and actually made me want to grapple with the complexities of these mysterious proteins that I sometimes hear about but shy away from. And again, I've found myself that creating a character of the proteins I work with sometimes helps to visualise the more complex interactions.

As an extension of this line of thought: how about turning this scenario into a screenplay or a ballet (something else I've considered with my own work)? It would be fun to do at a conference, for example. And you never know when you might gain an unexpected insight . . . .

Thanks, Olga! This was a great start to the day!


The Lobster




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comment:
Wonderful Approach!
by john toeppen

[Comment posted 2008-04-11 15:43:06]

When designing office copiers we would discuss the "motivation" for toner particles to jump from the developer roll to the electrostatic image. This proved to be a "silly but effective" way to visualize a complex process. Often our scientic formality can prevent us from having a comfortable understanding of complexity. Viewing problems from different perspectives is more than fun - it can be the path to deeper understanding. So, know when to hang loose dudes!