PSTPIP2

Last updated
PSTPIP2
Identifiers
Aliases PSTPIP2 , MAYP, proline-serine-threonine phosphatase interacting protein 2
External IDs OMIM: 616046 MGI: 1335088 HomoloGene: 69150 GeneCards: PSTPIP2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_024430

NM_013831
NM_177831

RefSeq (protein)

NP_077748

NP_038859

Location (UCSC) Chr 18: 45.98 – 46.07 Mb n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Proline-serine-threonine phosphatase-interacting protein 2 is an enzyme that in humans is encoded by the PSTPIP2 gene. [4] [5] This protein, also known as macrophage F-actin-associated and tyrosine phosphorylated protein (MAYP) is a member of the Pombe Cdc15 homology (PCH) family of proteins has been shown to coordinate membrane and cytoskeletal dynamics [6]

Contents

Function

Pstpip2 is selectively expressed in macrophages and macrophage precursors, [7] [8] and it is an actin bundling protein which regulates filopodia formation and macrophage motility [9]

Cytokine expression profile

PSTPIP2 deficiency leads to elevated levels of circulating inflammatory mediators in vivo. In asymptomatic mice, only MIP-1α and IL-6 are elevated, however symptomatic PSTPIP2-deficient mice have elevated levels of circulating IL-6, MIP-1α, TNF-α, CSF-1 and IP-10 [10] and decreased levels of IL-13 [11] [12]

Disease linkage

The missense mutation I282N leads to a macrophage-mediated autoinflammatory disease called Lupo Pstpip2 (Pstpip2Lupo/Lupo ). It is characterized by skin necrosis, inflammation of paws, ears and inflammatory bone resorption. [8] Another mutation in Pstpip2, L98P, was described in chronic multifocal osteomyelitis (cmo) mice. This disease is also autoinflammatory, and causes inflammatory infiltrate of polymorphonuclear leukocytes, macrophages, lymphocytes, plasma cells and osteoclasts. Later the infiltrate is replaced with new bone tissue which lead to tail kinks and hind-foot deformities. The cmo mice also develop ear inflammation in the epidermis, dermis and cartilage. [13]

Interactions

PSTPIP2 interacts with protein tyrosine phosphatases from the proline-, glutamic acid-, serine- and threonine-rich (PEST) family, [14] SHIP1 and Csk [15]

Related Research Articles

The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.

<span class="mw-page-title-main">Macrophage colony-stimulating factor</span> Mammalian protein found in humans

The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the placenta.

<span class="mw-page-title-main">PTPN11</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2.

<span class="mw-page-title-main">Tyrosine-protein kinase SYK</span>

Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene.

<span class="mw-page-title-main">Tyrosine kinase 2</span> Enzyme and coding gene in humans

Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.

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

Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.

<span class="mw-page-title-main">PTPN1</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the PTPN1 gene. PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type 2 diabetes. It has also been implicated in the development of breast cancer and has been explored as a potential therapeutic target in that avenue as well.

<span class="mw-page-title-main">Colony stimulating factor 1 receptor</span> Protein found in humans

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.

<span class="mw-page-title-main">PTPN22</span> Protein-coding gene in the species Homo sapiens

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a cytoplasmatic protein encoded by gene PTPN22 and a member of PEST family of protein tyrosine phosphatases. This protein is also called "PEST-domain Enriched Phosphatase" ("PEP") or "Lymphoid phosphatase" ("LYP"). The name LYP is used strictly for the human protein encoded by PTPN22, but the name PEP is used only for its mouse homolog. However, both proteins have similar biological functions and show 70% identity in amino acid sequence. PTPN22 functions as a negative regulator of T cell receptor (TCR) signaling, which maintains homeostasis of T cell compartment.

<span class="mw-page-title-main">INPP5D</span> Protein-coding gene in the species Homo sapiens

Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1(SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the INPP5D gene in humans. SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies.

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

Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.

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

Receptor-type tyrosine-protein phosphatase epsilon is an enzyme that in humans is encoded by the PTPRE gene.

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

Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene.

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

Receptor-type tyrosine-protein phosphatase S, also known as R-PTP-S, R-PTP-sigma, or PTPσ, is an enzyme that in humans is encoded by the PTPRS gene.

<span class="mw-page-title-main">PSTPIP1</span> Enzyme found in humans

Proline-serine-threonine phosphatase-interacting protein 1 is an enzyme that in humans is encoded by the PSTPIP1 gene.

<span class="mw-page-title-main">MTSS1</span> Protein-coding gene in the species Homo sapiens

Metastasis suppressor protein 1 is a protein that in humans is encoded by the MTSS1 gene. True to its name, it codes for a metastasis suppressor.

<span class="mw-page-title-main">PTPRD</span> Protein-coding gene in humans

Receptor-type tyrosine-protein phosphatase delta is an enzyme that, in humans, is encoded by the PTPRD gene.

<span class="mw-page-title-main">PTPN18</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein phosphatase non-receptor type 18 is an enzyme that in humans is encoded by the PTPN18 gene.

<span class="mw-page-title-main">PTPN21</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein phosphatase non-receptor type 21 is an enzyme that in humans is encoded by the PTPN21 gene.

Tensin was first identified as a 220 kDa multi-domain protein localized to the specialized regions of plasma membrane called integrin-mediated focal adhesions. Genome sequencing and comparison have revealed the existence of four tensin genes in humans. These genes appear to be related by ancient instances of gene duplication.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000152229 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. Wu Y, Dowbenko D, Lasky LA (November 1998). "PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase". The Journal of Biological Chemistry. 273 (46): 30487–96. doi: 10.1074/jbc.273.46.30487 . PMID   9804817.
  5. "Entrez Gene: PSTPIP2 proline-serine-threonine phosphatase interacting protein 2".
  6. Chitu V, Stanley ER (March 2007). "Pombe Cdc15 homology (PCH) proteins: coordinators of membrane-cytoskeletal interactions". Trends in Cell Biology. 17 (3): 145–56. doi:10.1016/j.tcb.2007.01.003. PMID   17296299.
  7. Yeung YG, Soldera S, Stanley ER (November 1998). "A novel macrophage actin-associated protein (MAYP) is tyrosine-phosphorylated following colony stimulating factor-1 stimulation". The Journal of Biological Chemistry. 273 (46): 30638–42. doi: 10.1074/jbc.273.46.30638 . PMID   9804836.
  8. 1 2 Grosse J, Chitu V, Marquardt A, Hanke P, Schmittwolf C, Zeitlmann L, Schropp P, Barth B, Yu P, Paffenholz R, Stumm G, Nehls M, Stanley ER (April 2006). "Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease". Blood. 107 (8): 3350–8. doi: 10.1182/blood-2005-09-3556 . PMC   1895761 . PMID   16397132.
  9. Chitu V, Pixley FJ, Macaluso F, Larson DR, Condeelis J, Yeung YG, Stanley ER (June 2005). "The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages". Molecular Biology of the Cell. 16 (6): 2947–59. doi: 10.1091/mbc.e04-10-0914 . PMC   1142438 . PMID   15788569.
  10. Chitu V, Ferguson PJ, de Bruijn R, Schlueter AJ, Ochoa LA, Waldschmidt TJ, Yeung YG, Stanley ER (September 2009). "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood. 114 (12): 2497–505. doi:10.1182/blood-2009-02-204925. PMC   2746474 . PMID   19608749.
  11. Doherty TM, Kastelein R, Menon S, Andrade S, Coffman RL (December 1993). "Modulation of murine macrophage function by IL-13". J. Immunol. 151 (12): 7151–60. doi:10.4049/jimmunol.151.12.7151. PMID   7903102.
  12. Martinez FO, Sica A, Mantovani A, Locati M (January 2008). "Macrophage activation and polarization". Front. Biosci. 13 (13): 453–61. doi: 10.2741/2692 . PMID   17981560.
  13. Chitu V, Ferguson PJ, de Bruijn R, Schlueter AJ, Ochoa LA, Waldschmidt TJ, Yeung YG, Stanley ER (September 2009). "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood. 114 (12): 2497–505. doi: 10.1182/blood-2009-02-204925 . PMC   2746474 . PMID   19608749.
  14. Veillette A, Rhee I, Souza CM, Davidson D (March 2009). "PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders". Immunological Reviews. 228 (1): 312–24. doi:10.1111/j.1600-065x.2008.00747.x. PMID   19290936. S2CID   30394426.
  15. Drobek A, Kralova J, Skopcova T, Kucova M, Novák P, Angelisová P, Otahal P, Alberich-Jorda M, Brdicka T (October 2015). "PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with Inhibitory Enzymes SHIP1 and Csk". Journal of Immunology. 195 (7): 3416–26. doi: 10.4049/jimmunol.1401494 . PMID   26304991.

Further reading