View source for Class III PI 3-kinase

You do not have permission to edit this page, for the following reason:

This IP address has been blocked from editing Wikipedia.
This does not affect your ability to read Wikipedia pages.

Most people who see this message have done nothing wrong. Some kinds of blocks restrict editing from specific service providers or telecom companies in response to recent abuse or vandalism, and can sometimes affect other users who are unrelated to that abuse. Review the information below for assistance if you do not believe that you have done anything wrong.

The IP address or range 44.197.0.0/16 has been blocked by ‪ST47‬ for the following reason(s):

The IP address that you are currently using has been blocked because it is believed to be a web host provider. To prevent abuse, web hosts may be blocked from editing Wikipedia.

You will not be able to edit Wikipedia using a web host provider because it hides your IP address, much like a proxy or VPN.

We recommend that you attempt to use another connection to edit. For example, if you use a proxy or VPN to connect to the internet, turn it off when editing Wikipedia. If you edit using a mobile connection, try using a Wi-Fi connection, and vice versa. If you are using a corporate internet connection, switch to a different Wi-Fi network. If you have a Wikipedia account, please log in.

If you do not have any other way to edit Wikipedia, you will need to request an IP block exemption.

How to appeal if you are confident that your connection does not use a web host's IP address:

If you are confident that you are not using a web host, you may appeal this block by adding the following text on your talk page:

{{unblock|reason=Caught by a web host block but this host or IP is not a web host. My IP address is _______. Place any further information here. ~~~~}}

. You must fill in the blank with your IP address for this block to be investigated. Your IP address can be determined here. Alternatively, if you wish to keep your IP address private you can use the unblock ticket request system. There are several reasons you might be editing using the IP address of a web host (such as if you are using VPN software or a business network); please use this method of appeal only if you think your IP address is in fact not a web host.

Administrators: The IP block exemption user right should only be applied to allow users to edit using web host in exceptional circumstances, and they should usually be directed to the functionaries team via email. If you intend to give the IPBE user right, a CheckUser needs to take a look at the account. This can be requested most easily at SPI Quick Checkuser Requests. Unblocking an IP or IP range with this template is highly discouraged without at least contacting the blocking administrator.

This block will expire on 07:24, 6 August 2027. Your current IP address is 44.197.176.145.

Even when blocked, you will usually still be able to edit your user talk page, as well as email administrators and other editors.

For information on how to proceed, please read the FAQ for blocked users and the guideline on block appeals. The guide to appealing blocks may also be helpful.

Other useful links: Blocking policy · Help:I have been blocked

You can view and copy the source of this page:

'''Class III PI 3-kinase''' is a subgroup of the enzyme family, [[phosphoinositide 3-kinase]] that share a common protein domain structure, substrate specificity and method of activation.

There is only one known class III PI 3-kinase, Vps34, which is also the only PI 3-kinase expressed in all [[eukaryotic]] cells. In humans it is encoded by the [[PIK3C3]] gene. In human cells Vps34 associates with a regulatory subunit, [[PIK3R4]](p150, Vps15).<ref>{{cite journal|author=Backer, J.M.|year=2008|title=The regulation and function of Class III PI3Ks: novel roles for Vps34|url=https://doi.org/10.1042/bj20071427|journal=Biochem. J.|volume=410|issue=1 |pages=1–17|doi=10.1042/bj20071427 |pmid=18215151 }}</ref>

==Substrate specificity==
Vps34 is more accurately described as a phosphatidylinositol 3-kinase. ''In vivo'' Vps34 can phosphorylate only [[phosphatidylinositol]] to form phosphatidylinositol (3)-phosphate ([[PtdIns(3)P]]).

==Functions==
Vps34 was first identified in a ''[[Saccharomyces cerevisiae]]'' (budding yeast) screen for proteins involved vesicle-mediated '''v'''acuolar '''p'''rotein '''s'''orting (hence Vps). A number of proteins containing a [[phosphoinositide binding domain]] specific for PtdIns(3)P that function in cellular protein trafficking have been identified.

Vps34 has been shown to interact with Vps15 (PIK3R4, p150), a protein kinase.  Vps15 can activate the lipid kinase activity of Vps34 and interact with [[RAB5A|Rab5]], which has been hypothesized to recruit the Vps34/15 complex to early [[endosome]]s. Vps15 has a [[myristoylation]] tag that associates the complex with the membrane.  The Vps34/15 complex also can interact with [[RAB7|Rab7]].  Together, the complex can function at early to late endosomes.

Vps34 has a [[calmodulin binding domain]], but its activity has been clearly shown to be calcium-independent in vitro and in vivo. The functional role of its interactions with [[calmodulin]] in vivo are not understood.

Vps34 activity is required for [[autophagy]] in yeast, and has been strongly implicated in this process in mammals. Vps34 has also been implicated in amino acid sensing.  Vps34 is necessary for [[mTORC1]] activity in response to amino acids in cultured cells, as [[siRNA]] knockdown completely inhibits mTORC1 signaling as determined by [[S6K]] phosphorylation.  Sequestration of the Vps34 product by [[FYVE domain]] overexpression also disrupts mTOR signaling. However, genetic ablation of Vps34 in ''[[Drosophila]]'' does not affect dTORC1 signaling. Thus, the role of Vps34 in amino acid signaling to mTORC1 remains controversial.

One recent paper suggested that the human ortholog is regulated by intracellular calcium, but this was later shown to be due to a calcium-independent inhibition of Vps34 by [[EGTA (chemical)|EGTA]], an effect not seen with other calcium chelators.

The mechanisms that regulate Vps34 activity in mammalian cells are not yet understood.

==See also==
* [[PX domain]]

==References==
{{reflist}}

== Literature ==
{{refbegin}}
* {{cite journal | vauthors = Stein RC | title = Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment | journal = Endocrine-Related Cancer | volume = 8 | issue = 3 | pages = 237–248 | date = September 2001 | pmid = 11566615 | doi = 10.1677/erc.0.0080237  }}
* {{cite journal | vauthors = Foster FM, Traer CJ, Abraham SM, Fry MJ | title = The phosphoinositide (PI) 3-kinase family | journal = Journal of Cell Science | volume = 116 | issue = Pt 15 | pages = 3037–3040 | date = August 2003 | pmid = 12829733 | doi = 10.1242/jcs.00609 }}
* {{cite journal | vauthors = Vanhaesebroeck B, Waterfield MD | title = Signaling by distinct classes of phosphoinositide 3-kinases | journal = Experimental Cell Research | volume = 253 | issue = 1 | pages = 239–254 | date = November 1999 | pmid = 10579926 | doi = 10.1006/excr.1999.4701 }}
{{refend}}

{{Kinases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

[[Category:EC 2.7.1]]

Pages transcluded onto the current version of this page (help):

Template:Cite journal (view source) (protected)
Template:Enzymes (view source) (template editor protected)
Template:Hlist/styles.css (view source) (protected)
Template:Kinases (view source) (semi-protected)
Template:Main other (view source) (protected)
Template:Navbox (view source) (template editor protected)
Template:Portal bar (view source) (template editor protected)
Template:Refbegin (view source) (template editor protected)
Template:Refbegin/styles.css (view source) (template editor protected)
Template:Refend (view source) (template editor protected)
Template:Reflist (view source) (protected)
Template:Reflist/styles.css (view source) (protected)
Module:Arguments (view source) (protected)
Module:Check for unknown parameters (view source) (protected)
Module:Citation/CS1 (view source) (protected)
Module:Citation/CS1/COinS (view source) (protected)
Module:Citation/CS1/Configuration (view source) (protected)
Module:Citation/CS1/Date validation (view source) (protected)
Module:Citation/CS1/Identifiers (view source) (protected)
Module:Citation/CS1/Utilities (view source) (protected)
Module:Citation/CS1/Whitelist (view source) (protected)
Module:Citation/CS1/styles.css (view source) (protected)
Module:Navbar (view source) (protected)
Module:Navbar/configuration (view source) (protected)
Module:Navbar/styles.css (view source) (protected)
Module:Navbox (view source) (template editor protected)
Module:Navbox/configuration (view source) (template editor protected)
Module:Navbox/styles.css (view source) (template editor protected)
Module:Portal (view source) (protected)
Module:Portal/images/b (view source) (template editor protected)
Module:Portal bar (view source) (template editor protected)
Module:Portal bar/styles.css (view source) (template editor protected)
Module:TableTools (view source) (protected)
Module:Yesno (view source) (protected)

Return to Class III PI 3-kinase.

Retrieved from "https://en.wikipedia.org/wiki/Class_III_PI_3-kinase"