Talk:Dephosphorylation

Improving the quality of this article

This article needs to be updated to include a greater range of information and to utilize sourced documents. Any images detailing the process of dephosphorylation would also add to the article.WeberOwl (talk) 03:33, 12 March 2013 (UTC)

This article can also be improved by including recent, high-quality, scholarly articles that describe new applications of this process. As a biochemistry and molecular biology stub, it can be improved by making this article mirror the phosphorylation page in terms of organization. MonopterusAlbus (talk) 11:06, 26 March 2013 (UTC)

Comments from Er1cah0p3

This article is well written with no obvious errors in spelling or grammar. The lead section makes sense and the article flows nicely. The references are good with no plagarism. It looks like expansion is planned for the Post-translational Modifications and Dephosphoryaltion in Plants sections which will add greatly to the article. I feel that an image would also be an asset to the article if one can be found/created. A visual aid may help tremendously. I also wonder if there could be more expanison of the function of dephosphorylation in extracellular signaling as mentioned in the first reference listed for the article. Overall the article is coming along nicely.Er1cah0p3 (talk) 18:15, 11 April 2013 (UTC)

Thanks for the suggestions. I agree that working in a section (or at least* some information) on post-translational modifications would be useful, though I'm unsure if it's worthwhile to have an entire section dedicated to dephosphorylation in plants (searching for good primary sources on this didn't turn up much). An image would add a lot to the quality and feel of the page, I'll see what I can come up with that would be appropriate and add information, instead of just taking up space for the sake of having a picture.WeberOwl (talk) 01:24, 25 April 2013 (UTC)

Primary literature sources might be the best bet for finding a graphic showing the mechanism of dephosphorylation. Unfortunately, Krebs' article came out in 1979, so it is not yet in the public domain. Perhaps there is a similar diagram within WikiMedia. WeberOwl, do you think you could help me with images in your sandbox? MonopterusAlbus (talk) 01:45, 25 April 2013 (UTC)

There are lots of good figures in the literature, but whatever we use needs to be categorized as available for open use. The image I've currently posted, which shows a phosphorylation/dephosphorylation cycle, meets this requirement. WeberOwl (talk) 16:30, 26 April 2013 (UTC)

Really great work so far! The article is much improved. The function section has added necessary information and the role in disease is a nice addition. I think it is really coming along nicely and I think the flow between sections is good. Some additional references could be added into the lead section but other than that this is strong work.Er1cah0p3 (talk) 00:33, 2 May 2013 (UTC)

Thanks for your comments throughout the article editing process. I'm going to work in some more references and details to wrap up incorporation of your suggestions.WeberOwl (talk) 21:12, 9 May 2013 (UTC)

Comments from Cdunca12

Phosphorylation and dephosphorylation of hydroxyl groups belonging to neutral but polar amino acids such as serine, threonine, and tyrosine within specific target proteins is a fundamental part of the regulation of every physiologic process. Phosphorylation involves the covalent modification of the hydroxyl with a phosphate group through the nucleophilic attack of the alpha phosphate in ATP by the oxygen in the hydroxyl. Dephosphorylation involves removal of the phosphate group through a hydration reaction by addition of a molecule of water and release of the original phosphate group, regenerating the hydroxyl. Both processes are reversible and either mechanism can be used to activate or deactivate a protein. Phosphorylation of a protein produces many biochemical effects, such as changing its conformation to alter its binding to a specific ligand to increase or reduce its activity. Phosphorylation and dephosphorylation can be used on all types of substrates, such as structural proteins, enzymes, membrane channels, signaling molecules, and other kinases and phosphatases. The deregulation of phosphorylation can lead to disease. The importance of phosphorylation in all biological processes is the reason why this topic is very notable. (1,2)

Because phosphorylation is reversible, the descriptions in each section should elaborate on both phosphorylation and dephosphorylation.

1. Lead Section -Only describes dephosphorylation without putting it into context with phosphorylation. Description for the mechanism of dephosphorylation is incomplete and inaccurate. Be careful with choice of words such as “opposite” and “featured”.

-Suggestion: a. Basic explanation and mechanism of phosphorylation and dephosphorylation and the enzymes involved. b. Notability - explain the importance of phosphorylation and dephosphorylation in the regulation of every physiologic process. c. Provide basic example of how disease can develop from deregulation of reversible phosphorylation.

2. History Section -Can be placed at the end. The paper by Raju TN describes of research on glycogen metabolism that elucidated the importance of phosphorylation of proteins. The details of this research highlighting this discovery should be elaborated and how these findings sparked new research on the phosphorylation of many other types of proteins in various biological processes. (5)

3. Function or Mechanism Section -Post-translational modification subsection can describe more details on this process with how the newly synthesized peptide is released from the ribosome and modified in endoplasmic reticulum, ER, and golgi apparatus. The explanation for dephosphorylation as a way of “modifying behavior of a protein, often by activating..” needs a clearer elaboration. Provide specific examples with names of proteins and their mechanism. “…phophate groups may be removed from amino acids” needs a schematic. - Dephosphorylation of ATP subsection requires more elaboration. The first two sentences are too general. Describe how 30.5 kJ/mol of energy is released. Show a schematic. Remaining sentences are not clear. What is oxidative phosphorylation? Describe this or include a link for this term. -Dephosphorylation in other reactions subsection. Describe the pathways the compounds are a part of and the process of their dephophorylation that would generate the change in free energy.

-Suggestions for subsections under “Function”: -Explanation of phosphorylation and dephosphorylation by demonstrating the chemistry through a schematic, including a kinase, which phosphorylates, followed by a phosphatase, which reverses the reaction. -Subsection on different types of phosphorylation/dephosphorylation of protein substrates and the function that is carried out (switch the protein on or off). Include a schematic, showing catalytic domains of kinase and phosphatase and how the chemistry is carried out with specific residues of the protein in the catalytic site of kinase and phosphatase and how this will inactivate or amplify the specific reaction or downstream cell signalling. -Subsection on different protein phosphatase families (4).

4. Laboratory Applications can be renamed as Research Applications. Elaborate on the specific techniques.

5. Pathology Section -Describe specific mutations found in phosphatases and how the diseases that result. (3)

6. Clinical Section -Describe protein targets in specific diseases that have been found to be useful for certain drugs.

-Provide additional sourced content and references.

-Include more links on key terms.

References: 1) Lodish, Harvey et al. Molecular Cell Biology. New York, NY: Freeman, 2012. P. 90. 2) Bononi, Angela, et al. (2011). “Protein Kinases and Phosphatases in the Control of Cell Fate”. Enzyme Research 2011. PMID 21904669. 3) Zhang, Qingxiu, and Claret, Francois X. (2011). “Phosphatases: The new Brakes for Cancer Development?”. Enzyme Research 2012. 4) Mustelin, T. (2007). “A brief introduction to the protein phosphatase families”. Methods Mol Biol 365: 9-22. 5) Tarrant, Mary Katherine and Cole, Phillip A. (2009). “The Chemical Biology of Protein Phosphorylation”. Annual Review of Biochemistry 78: 797-825. (Refer to the introduction for explanation of discovery of phosphorylation). Cdunca12 08:08, 16 April 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

I really appreciate the time you spent in putting together these proposed revisions. I'm sure we'll achieve Good Article status once all of them are implemented. Thanks again! MonopterusAlbus (talk) 01:58, 25 April 2013 (UTC)

Thanks* for all of the feedback and suggestions, it's a big help. Your summary of dephosphorylation contains some good points, and I might try to work them directly in to the article. Going section by section is a great way of providing the editor with things the reader would like to see.WeberOwl (talk) 01:44, 25 April 2013 (UTC)

Does anybody else have input concerning how often phosphorylation should be mentioned alongside descriptions of dephosphorylation? I think that it should be mentioned in the overview sections, but don't see the value in always describing in counter to dephosphorylation. A separate phosphorylation cycle article might be better for that. WeberOwl (talk) 16:50, 26 April 2013 (UTC)

I think you're right, the focus here should be on the dephosphorylation process. You're on the right track! Keilana|^{Parlez ici} 18:47, 26 April 2013 (UTC)

I think you have done a really fantastic job at improving this article so far. It has a lot of important and relevant information. No need to compare phosphorylation and dephosphorylation side-by-side in every paragraph. The background and/or function sections will suffice.Cdunca12 06:23, 6 May 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Bold and italics, all right! Thanks for your comments as I edited the article, in particular your first suggestions were really useful.WeberOwl (talk) 21:14, 9 May 2013 (UTC)

No problem. Thanks for working so hard on this great article. Have a nice summer!Cdunca12 23:50, 10 May 2013 (UTC) — Preceding unsigned comment added by Cdunca12 (talk • contribs)

Review from klortho

• Comments by Cdunca12 above are outstanding. Please try to implement as many of these as you can.
• The article is too short. There should be significantly more content that this by now. Note that Cdunca's review of your article is much longer than this article itself.
• I also agree with Er1cah0p3 (and Cdunca12 also mentions): it should be possible to find some images / schematics to go along with this article.

Klortho (talk) 14:44, 21 April 2013 (UTC)

I found an image and have added it to the page, and plan on adding more as I can find them. Currently I have some chemical equations, would these be better if converted to schematics?WeberOwl (talk) 01:42, 25 April 2013 (UTC)

The SMG/UPF image might be too specific, as it does not clearly show which enzyme is phosphorylating or dephosphorylating. This can be remedied with a better caption or a different image. MonopterusAlbus (talk) 01:52, 25 April 2013 (UTC)

Comments from jmudukes88

• Lead Section

1. My first observation was the lack of references used in the lead section. I would definitely look to add this. Recall, that Wiki prefers a reference every 1 or 2 sentences. This is obviously too much, but try to reference at least once in each of those paragraphs.
2. I like the first paragraph of the lead section. After you mention “… dephosphorylation is the conversion of ATP to ADP and inorganic phosphate”, it seems to be a good time to actually show this in an equation. I know this may be tough, but maybe you can take this from other sites to use as a thumbnail?
3. Link enzyme in 2nd paragraph of lead.
4. The end of the 2nd lead paragraph seems like another good area to show the chemical equation of changes w/ the enzyme included.

• History section

1. Maybe elaborate on the discovery of reversible protein phosphorylation a bit more (like a brief line of how?).

• Function section

1. For the 1st sentence, add dashes at ends of “but polar"... Commas work too, but the dash would emphasize "polar" more as well as keeping the sentence clean (since commas are used afterwards). For example, "… hydroxyl groups belonging to neutral- but polar- amino acids such as serine, threonine…"
2. Add links to serine, threonine, etc. This would enable the user to see the chemical structures of these amino acids and see how they are neutral.
3. Link nucleophilic attack, conformation, ligand, and maybe activity. Also, substrates, membrane channels, signaling molecules.
4. Overall, I would look to add links throughout the article, especially when terms are first used. They don't need to be linked the second time, unless it is much further into an article or needs emphasis.

• Posttranslation modification section

1. Maybe change that first sentence to the active voice? It’s currently: “During the synthesis of proteins, polypeptide chains, which are created by ribosomes translating mRNA, must be processed before assuming a mature conformation.”
2. My suggestion is: "Polypeptide chains, which are created by ribosomes translating mRNA, must be processed during protein synthesis to assume a mature conformation."
3. Maybe include an example of posttranslational modification w/ the use of dephosphorylation? This would be a good section for this, and explain how the change affects function.

• Dephosphorylation of ATP section

1. 2nd sentence- “That nonspontaneous reactions”… could be changed to “The ability to couple nonspontaneous reactions to the highly spontaneous…”. This would help the sentence flow a bit better.
2. If you have time, make that chemical equation you have mentioned in the same format as other Wiki pages
3. In regards to the table under Dephosphorylation in other reactions: All of the changes in free energy are positive, except for one (PEP). This seems to be the only spontaneous change. How come in the prior section ("dephoshporylation of ATP") you mentioned nonspontaneous reactions make the overall change in free energy spontaneous? This table indicates that more compounds become less spontaneous due to the change in free energy. Maybe, add to the brief summary how this is so.

• Role of dephosphorylation in disease section

1. Look to reference these findings a bit more- obviously, using your reference by Gong et al. (1994).
2. To expand your article as the suggestion of others, you can add more recent articles/examples as well

• Research applications section

1. Look to add more to this section. I liked how you had examples in your prior section, "Role of dephosphorylation in disease". Maybe add some examples of dephosphorylating phosphatases to avoid ligation of the cut ends of a vector.
2. For the last sentence of this section, you have mentioned “These alkaline phosphatases…” with no prior mentioning of alkaline phosphatases. Instead, how about saying, “One example of a dephosphorylating phosphatase is the calf-intestinal alkaline phosphate, CIP. This is just a part of a family of alkaline phosphatases often sourced naturally.”

Overall, it looks like the article is pretty nicely setup in terms of flow. It can definitely use a bit more context in sections, which can be added through giving more examples (w/ their respective references). I have specified what sections can use this above. The Lead section follows guidelines with the exception of no citation, but all of the content that is referenced seems to match up fine. I would recommend adding some material to establish how dephosphorylation is important to systems. Recall this requirement in the second paragraph of lead section guidelines. There is no excessive use of jargon through the article. However, several areas can be linked to other Wiki pages, which can be found in my comments above. I only made suggestions for links in one section, but the whole article can use more links excluding the Lead. Each section is coherent with all of the content in accord with the section title from what I read. The areas I have check did not have excessive use of “too-close paraphrasing” and the editors avoid plagiarism in this manner as well. Jmudukes88 (talk) 00:37, 28 April 2013 (UTC)

Thanks for the feedback. I agree with a lot of your points and your post will be a great reference for the next set of revisions. Something I'm curious about though (calling all Wiki Experts!) is the use of citations in the introduction section. A lot of "good quality" articles I've seen have ample citations throughout the body of the article, but few to none in the introduction? Is this considered OK, or even preferable, since everything in the introduction should in theory be discussed later on in the article?WeberOwl (talk) 00:43, 2 May 2013 (UTC)

Yeah, I started to notice this too just as you have mentioned. I will say, however, the lead section Wiki page does state "The emphasis given to material in the lead should roughly reflect its importance to the topic, according to reliable, published sources...". There is also a "Citation" section on that same page. Here's a link to the page, lead section. Jmudukes88 (talk) 22:51, 5 May 2013 (UTC)

I guess it's better to be on the safe side and add some citations in - I can't imagine that making sure all information is properly referenced will get any negative feedback from the wikipedia community.WeberOwl (talk) 20:42, 6 May 2013 (UTC)

Hi guys! For those of you that didn't read the information on the lead section, the aim is to avoid redundancy in citations. The information presented in the lead appears elsewhere in the article in detail, so it is not necessary to cite twice. Here's the paragraph on citations you mentioned. Hopefully this clears everything up:

"The lead must conform to verifiability and other policies. The verifiability policy advises that material that is challenged or likely to be challenged, and quotations, should be supported by an inline citation. Because the lead will usually repeat information that is in the body, editors should balance the desire to avoid redundant citations in the lead with the desire to aid readers in locating sources for challengeable material. Leads are usually written at a greater level of generality than the body, and information in the lead section of non-controversial subjects is less likely to be challenged and less likely to require a source; there is not, however, an exception to citation requirements specific to leads. The necessity for citations in a lead should be determined on a case-by-case basis by editorial consensus. Complex, current, or controversial subjects may require many citations; others, few or none. The presence of citations in the introduction is neither required in every article nor prohibited in any article."

MonopterusAlbus (talk) 06:10, 7 May 2013 (UTC)

I will confirm that everything mentioned in the introduction is discussed and cited at later points in the article. WeberOwl (talk) 21:15, 9 May 2013 (UTC)

Comments from Jessicalau90

Overall, the article has a lot of good improvements. I think the comments and feedback provided by the other reviewers are definitely very informative and you could use most of their suggestions to improve the article.

Here's some of my suggestions. Under the history section, I think you could expand on it more. Perhaps also add an image of Edwin Krebs and Edmond Fischer? How was dephosphorylation discovered?

Under the function section, I would also add more images- image of a dephosphorylation reaction/ nucleophilic attack of alpha phosphate in ATP by oxygen in the hydroxyl. There was mention in the first part: "The deregulation of phosphorylation can lead to disease." Maybe list the kinds of diseases (such as Alzheimer's and Cardiac disease) that can occur in this portion and then elaborate on them in the section "role of dephosphorylation in disease". I would also add an image of hydrolase if possible since it is a key enzyme. In the subsection posttranslational modification, maybe you can elaborate on how dephosphorylation can activate or inactive an enzyme. Provide some examples. Dephosphorylation of ATP is crucial in many processes-glycolysis, gluconeogenesis so again, maybe use those as examples. The sections role of dephosphorylation in disease and research applications can also be expanded upon.

In general, good article, but could use more images, examples and specifics and elaborate more on the different sections, like what the other reviewers have mentioned. Hope this was useful! Jessicalau90 (talk) 18:59, 2 May 2013 (UTC)

I like your suggestion to mention the diseases earlier in the article, and then elaborate in more detail in the disease section. I'll be sure to make some changes to reflect this. I'm hesitant to add a picture of Krebs or Fisher, since it doesn't add much to the content of the article, and I don't want to have pictures just for the sake of having pictures. However for the dephosphorylation reaction, if I can find any open source image along the lines of what you've described I will definitely include it. WeberOwl (talk) 19:45, 2 May 2013 (UTC)