Pleckstrin
| Pleckstrin-1 | |||||||
|---|---|---|---|---|---|---|---|
 Ribbon diagram of the C-terminal pleckstrin homology domain of pleckstrin-1 bound to inositol 1,2,3,4,5-pentaphosphate (PDBID 2I5C) | |||||||
| Identifiers | |||||||
| Symbol | PLEK | ||||||
| NCBI gene | 5341 | ||||||
| HGNC | 9070 | ||||||
| OMIM | 173570 | ||||||
| RefSeq | NM_002664 | ||||||
| UniProt | P08567 | ||||||
| Other data | |||||||
| Locus | Chr. 2p13.3 | ||||||
| |||||||
| Pleckstrin-2 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | PLEK2 | ||||||
| NCBI gene | 26499 | ||||||
| HGNC | 19238 | ||||||
| OMIM | 608007 | ||||||
| PDB | 1X1G | ||||||
| RefSeq | NM_016445 | ||||||
| UniProt | Q9NYT0 | ||||||
| Other data | |||||||
| Locus | Chr. 14q23.3q24.1 | ||||||
| Wikidata | Q18038260 | ||||||
| |||||||
Pleckstrinsare a family ofproteinsfound inplatelets[1]and other cells. The name derives fromplatelet andleukocyteCkinasesubstrate and theKSTRstring ofamino acids.The prototype protein, now called pleckstrin-1, was first identified in 1979 as the major substrate ofprotein kinase Cin platelets.[2]The homolog pleckstrin-2 is more widely expressed in tissues.[3]
Thepleckstrin homology domain(PH domain) was named after pleckstrin-1.[2]
Sequence and structure
[edit]Both pleckstrin-1 and pleckstrin-2 contain two pleckstrin homology domains, separated by a centraldishevelled-Egl10-pleckstrin (DEP) domain.Pleckstrin-1 isphosphorylatedby protein kinase C on threeserineandthreonineresidues located between the first pleckstrin homology domain and the DEP domain;[2]pleckstrin-2 is not a substrate for protein kinase C.[2][4]The two proteins share 65%sequence homology[2]and have a size of about 47kilodaltons.[5]
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.[2]
Functions
[edit]Pleckstrins are involved in rearranging theactin cytoskeletonin such processes asplatelet activation,erythropoeisis,and cell spreading by extension offilopodiaandlamellipodia.[3]Pleckstrin-1 is believed to become activated by protein kinase C phosphorylation, which results in binding of the membrane lipidphosphatidylinositol 3,4-bisphosphate.[2]Interactions withintegrinsand theRacGTPase then lead to reorganization of the actin cytoskeleton.[3]Pleckstrin-2 also binds toinositol phospholipids,but interacts directly withF-actin,unlike pleckstrin-1.[3]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.[2]It also occurs in immune cells such asmacrophagesandneutrophils,[2][3]where it is involved in formation ofphagosomesand the secretion of proinflammatorycytokines.[3]
Pleckstrin-2 has roles in cell spreading, inflammation, erythropoeisis, andtumorigenesis.In lymphocytes, it is involved inPI3 kinase-mediatedimmune synapseformation. Pleckstrin-2 also mediates cytoskeletal changes involved in proliferation oferythroblastsearly in erythropoeisis. It is also believed to be crucial in theepithelial-to-mesenchymal transitionin tumor metastasis, and pleckstrin-2 is known to be overexpressed in a variety of cancers.[3]
References
[edit]- ^Harlan JE, Hajduk PJ, Yoon HS, Fesik SW (September 1994). "Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate".Nature.371(6493): 168–170.Bibcode:1994Natur.371..168H.doi:10.1038/371168a0.hdl:10356/94313.PMID8072546.S2CID4321763.
- ^abcdefghiEdlich C, Stier G, Simon B, Sattler M, Muhle-Goll C (February 2005)."Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin".Structure.13(2): 277–286.doi:10.1016/j.str.2004.11.012.PMID15698571.
- ^abcdefgWang G, Zhou Q, Xu Y, Zhao B (2021)."Emerging Roles of Pleckstrin-2 Beyond Cell Spreading".Frontiers in Cell and Developmental Biology.9:768238.doi:10.3389/fcell.2021.768238.PMC8637889.PMID34869363.
- ^Hu MH, Bauman EM, Roll RL, Yeilding N, Abrams CS (July 30, 1999)."Pleckstrin 2, a widely expressed paralog of pleckstrin involved in actin rearrangement".J Biol Chem.274(31): 21515–21518.doi:10.1074/jbc.274.31.21515.PMID10419454.
- ^"PLEK - Pleckstrin - Homo sapiens (Human)".Uniprot.EMBI-EBL.Retrieved18 Mar2024.
External links
[edit]- pleckstrinat the U.S. National Library of MedicineMedical Subject Headings(MeSH)