Pleckstrin

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Pleckstrin-1
2I5C pleckstrin.png
Ribbon diagram of the C-terminal pleckstrin homology domain of pleckstrin-1 bound to inositol 1,2,3,4,5-pentaphosphate (PDB ID 2I5C)
Identifiers
SymbolPLEK
NCBI gene 5341
HGNC 9070
OMIM 173570
RefSeq NM_002664
UniProt P08567
Other data
Locus Chr. 2 p13.3
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Structures Swiss-model
Domains InterPro
Pleckstrin-2
Identifiers
SymbolPLEK2
NCBI gene 26499
HGNC 19238
OMIM 608007
PDB 1X1G
RefSeq NM_016445
UniProt Q9NYT0
Other data
Locus Chr. 14 q23.3q24.1
Wikidata Q18038260
Search for
Structures Swiss-model
Domains InterPro

Pleckstrins are a family of proteins found in platelets [1] and other cells. The name derives from platelet and leukocyte 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. [2] The homolog pleckstrin-2 is more widely expressed in tissues. [3]

Contents

The pleckstrin homology domain (PH domain) was named after pleckstrin-1. [2]

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; [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 47 kilodaltons. [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

Pleckstrins are involved in rearranging the actin cytoskeleton in such processes as platelet activation, erythropoeisis, and cell spreading by extension of filopodia and lamellipodia. [3] Pleckstrin-1 is believed to become activated by protein kinase C phosphorylation, which results in binding of the membrane lipid phosphatidylinositol 3,4-bisphosphate. [2] Interactions with integrins and the Rac GTPase then lead to reorganization of the actin cytoskeleton. [3] Pleckstrin-2 also binds to inositol phospholipids, but interacts directly with F-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 as macrophages and neutrophils, [2] [3] where it is involved in formation of phagosomes and the secretion of proinflammatory cytokines. [3]

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. [3]

Related Research Articles

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<span class="mw-page-title-main">Phosphatidylinositol 4,5-bisphosphate</span> Chemical compound

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<span class="mw-page-title-main">Pleckstrin homology domain</span> Protein domain

Pleckstrin homology domain or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.

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<span class="mw-page-title-main">TEC (gene)</span> Human gene

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<span class="mw-page-title-main">PLEKHA1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">SH2B3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PLEK2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Rho-associated protein kinase</span>

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References

  1. ↑ 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 . PMID   8072546. S2CID   4321763.
  2. 1 2 3 4 5 6 7 8 9 Edlich 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 . PMID   15698571.
  3. 1 2 3 4 5 6 7 Wang 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 . PMC   8637889 . PMID   34869363.
  4. ↑ 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 . PMID   10419454.
  5. ↑ "PLEK - Pleckstrin - Homo sapiens (Human)". Uniprot. EMBI-EBL. Retrieved 18 Mar 2024.
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