{{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 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 | 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 found in platelets<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 '''C''' kinase substrate and the '''KSTR''' string of amino acids. The prototype protein, now called pleckstrin-1, was first identified in 1979 as the major substrate of 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 (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. Pleckstrin-1 is phosphorylated by protein kinase C on three serine and 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<ref name=Edlich /> and have a size of about 47 kilodaltons.<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 in such processes as platelet activation, erythropoeisis, and cell spreading by extension of filopodia and 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.<ref name=Edlich /> Interactions with integrins and the Rac GTPase then lead to reorganization of the actin cytoskeleton.<ref name=Wang /> Pleckstrin-2 also binds to inositol phospholipids, but interacts directly with 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 and neutrophils,<ref name = Edlich /><ref name = Wang /> where it is involved in formation of phagosomes and the secretion of proinflammatory cytokines.<ref name=Wang />
Pleckstrin-2 has roles in cell spreading, inflammation, erythropoeisis, and tumorigenesis. In lymphocytes, it is involved in PI3 kinase-mediated immune synapse formation. Pleckstrin-2 also mediates cytoskeletal changes involved in proliferation of erythroblasts early in erythropoeisis. It is also believed to be crucial in the 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}}
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Category:Proteins