# Pleckstrin

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> Markdown URL: https://mediated.wiki/source/Pleckstrin.md
> Source: https://en.wikipedia.org/wiki/Pleckstrin
> Source revision: 1314962844
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{{Short description|Protein family}}
{{cs1 config |name-list-style=vanc|display-authors=6}}
{{protein
|Name=Pleckstrin-1
|caption=Ribbon diagram of the C-terminal pleckstrin homology domain of pleckstrin-1 bound to inositol 1,2,3,4,5-pentaphosphate ([PDB](/source/Protein_data_bank) ID 2I5C)
|image=2I5C pleckstrin.png
|width=
|HGNCid=9070
|Symbol=PLEK
|AltSymbols=
|EntrezGene=5341
|OMIM=173570
|RefSeq=NM_002664
|UniProt=P08567
|PDB=
|ECnumber=
|Chromosome=2
|Arm=p
|Band=13.3
|LocusSupplementaryData=
}}
{{Infobox protein
| name = [Pleckstrin-2](/source/PLEK2)
| AltNames =
| image = 
| width = 
| caption = 
| Symbol = PLEK2
| AltSymbols =
| EntrezGene = 26499
| HGNCid = 19238
| OMIM = 608007
| PDB = 1X1G
| RefSeq = NM_016445
| UniProt = Q9NYT0
| ECnumber = 
| Chromosome = 14
| Arm = q
| Band = 23.3
| LocusSupplementaryData = q24.1
| Wikidata = Q18038260
}}
'''Pleckstrins''' are a family of [proteins](/source/proteins) found in [platelet](/source/platelet)s<ref>{{cite journal | vauthors = Harlan JE, Hajduk PJ, Yoon HS, Fesik SW | title = Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate | journal = Nature | volume = 371 | issue = 6493 | pages = 168–170 | date = September 1994 | pmid = 8072546 | doi = 10.1038/371168a0 | bibcode = 1994Natur.371..168H | hdl-access = free | s2cid = 4321763 | hdl = 10356/94313 }}</ref> and other cells. The name derives from '''p'''latelet and ['''le'''ukocyte](/source/leukocyte) '''C''' [kinase](/source/kinase) substrate and the '''KSTR''' string of [amino acid](/source/amino_acid)s.  The prototype protein, now called pleckstrin-1, was first identified in 1979 as the major substrate of [protein kinase C](/source/protein_kinase_C) in platelets.<ref name=Edlich>{{cite journal | vauthors = Edlich C, Stier G, Simon B, Sattler M, Muhle-Goll C | title = Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin | journal = Structure | volume = 13 | issue = 2 | pages = 277–286 | date = February 2005 | pmid = 15698571 | doi = 10.1016/j.str.2004.11.012 | doi-access = free }}</ref>  The homolog pleckstrin-2 is more widely expressed in tissues.<ref name=Wang>{{cite journal | vauthors = Wang G, Zhou Q, Xu Y, Zhao B | title = Emerging Roles of Pleckstrin-2 Beyond Cell Spreading | journal = Frontiers in Cell and Developmental Biology | volume = 9 | article-number = 768238 | date = 2021 | pmid = 34869363 | doi = 10.3389/fcell.2021.768238 | doi-access = free | pmc = 8637889 }}</ref>

The [pleckstrin homology domain](/source/pleckstrin_homology_domain) (PH domain) was named after pleckstrin-1.<ref name=Edlich />

==Sequence and structure==

Both pleckstrin-1 and pleckstrin-2 contain two pleckstrin homology domains, separated by a central [dishevelled-Egl10-pleckstrin (DEP) domain](/source/DEP_domain).  Pleckstrin-1 is [phosphorylated](/source/protein_phosphorylation) by protein kinase C on three [serine](/source/serine) and [threonine](/source/threonine) residues located between the first pleckstrin homology domain and the DEP domain;<ref name=Edlich /> pleckstrin-2 is not a substrate for protein kinase C.<ref name=Edlich /><ref name=Hu>{{cite journal | vauthors = Hu MH, Bauman EM, Roll RL, Yeilding N, Abrams CS | title = Pleckstrin 2, a widely expressed paralog of pleckstrin involved in actin rearrangement| journal = J Biol Chem | volume = 274 | issue = 31 | pages = 21515–21518 | date = July 30, 1999 | pmid = 10419454 | doi = 10.1074/jbc.274.31.21515  | doi-access = free }}</ref>  The two proteins share 65% [sequence homology](/source/sequence_homology)<ref name=Edlich /> and have a size of about 47 [kilodalton](/source/kilodalton)s.<ref name=Uniprot>{{cite web |url=https://www.uniprot.org/uniprotkb/P08567/entry |title=PLEK - Pleckstrin - Homo sapiens (Human) |date= |website=Uniprot |publisher=EMBI-EBL |access-date=18 Mar 2024 |quote=}}</ref>

As of 2024, no high-resolution three-dimensional structure has been solved for full-length pleckstrin, but the structures of the individual domains of both pleckstrin-1 and -2 have been published.<ref name=Edlich />

== Functions ==

Pleckstrins are involved in rearranging the [actin cytoskeleton](/source/actin_cytoskeleton) in such processes as [platelet activation](/source/platelet_activation), [erythropoeisis](/source/erythropoeisis), and cell spreading by extension of [filopodia](/source/filopodia) and [lamellipodia](/source/lamellipodia).<ref name = Wang />  Pleckstrin-1 is believed to become activated by protein kinase C phosphorylation, which results in binding of the membrane lipid [phosphatidylinositol 3,4-bisphosphate](/source/phosphatidylinositol_3%2C4-bisphosphate).<ref name=Edlich />  Interactions with [integrins](/source/integrins) and the [Rac](/source/Rac_(GTPase)) GTPase then lead to reorganization of the actin cytoskeleton.<ref name=Wang />   Pleckstrin-2 also binds to [inositol phospholipid](/source/inositol_phospholipid)s, but interacts directly with [F-actin](/source/F-actin), unlike pleckstrin-1.<ref name=Wang />  Since pleckstrin-2 is expressed in a wider variety of cell types, its biological roles are more diverse than those of pleckstrin-1.

Pleckstrin-1 is a key protein in the membrane remodelling processes that occur during platelet activation.<ref name=Edlich />  It also occurs in immune cells such as [macrophages](/source/macrophages) and [neutrophils](/source/neutrophils),<ref name = Edlich /><ref name = Wang /> where it is involved in formation of [phagosomes](/source/phagosomes) and the secretion of proinflammatory [cytokines](/source/cytokines).<ref name=Wang />

Pleckstrin-2 has roles in cell spreading, inflammation, erythropoeisis, and [tumorigenesis](/source/tumorigenesis).  In lymphocytes, it is involved in [PI3 kinase](/source/PI3_kinase)-mediated [immune synapse](/source/immune_synapse) formation.  Pleckstrin-2 also mediates cytoskeletal changes involved in proliferation of [erythroblasts](/source/erythroblasts) early in erythropoeisis.  It is also believed to be crucial in the [epithelial-to-mesenchymal transition](/source/epithelial-to-mesenchymal_transition) in tumor metastasis, and pleckstrin-2 is known to be overexpressed in a variety of cancers.<ref name=Wang />

== References ==
{{Reflist}}

== External links ==
* {{MeshName|pleckstrin}}

{{Authority control}}

Category:Proteins

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Adapted from the Wikipedia article [Pleckstrin](https://en.wikipedia.org/wiki/Pleckstrin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Pleckstrin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.