Biology:PSTPIP2
 Generic protein structure example |
Proline-serine-threonine phosphatase-interacting protein 2 is an enzyme that in humans is encoded by the PSTPIP2 gene.[1][2] 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 [3]
Function
Pstpip2 is selectively expressed in macrophages and macrophage precursors,[4][5] and it is an actin bundling protein which regulates filopodia formation and macrophage motility[6]
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[7] and decreased levels of IL-13[8][9]
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.[5] 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.[10]
Interactions
PSTPIP2 interacts with protein tyrosine phosphatases from the proline-, glutamic acid-, serine- and threonine-rich (PEST) family,[11] SHIP1 and Csk[12]
References
- ↑ "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. November 1998. doi:10.1074/jbc.273.46.30487. PMID 9804817.
- ↑ "Entrez Gene: PSTPIP2 proline-serine-threonine phosphatase interacting protein 2". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=9050.
- ↑ "Pombe Cdc15 homology (PCH) proteins: coordinators of membrane-cytoskeletal interactions". Trends in Cell Biology 17 (3): 145–56. March 2007. doi:10.1016/j.tcb.2007.01.003. PMID 17296299.
- ↑ "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. November 1998. doi:10.1074/jbc.273.46.30638. PMID 9804836.
- ↑ 5.0 5.1 "Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease". Blood 107 (8): 3350–8. April 2006. doi:10.1182/blood-2005-09-3556. PMID 16397132.
- ↑ "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. June 2005. doi:10.1091/mbc.e04-10-0914. PMID 15788569.
- ↑ "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood 114 (12): 2497–505. September 2009. doi:10.1182/blood-2009-02-204925. PMID 19608749.
- ↑ "Modulation of murine macrophage function by IL-13". J. Immunol. 151 (12): 7151–60. December 1993. doi:10.4049/jimmunol.151.12.7151. PMID 7903102.
- ↑ "Macrophage activation and polarization". Front. Biosci. 13 (13): 453–61. January 2008. doi:10.2741/2692. PMID 17981560.
- ↑ "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood 114 (12): 2497–505. September 2009. doi:10.1182/blood-2009-02-204925. PMID 19608749.
- ↑ "PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders". Immunological Reviews 228 (1): 312–24. March 2009. doi:10.1111/j.1600-065x.2008.00747.x. PMID 19290936.
- ↑ "PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with Inhibitory Enzymes SHIP1 and Csk". Journal of Immunology 195 (7): 3416–26. October 2015. doi:10.4049/jimmunol.1401494. PMID 26304991.
Further reading
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. January 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "Yeast two-hybrid identification of prostatic proteins interacting with human sex hormone-binding globulin". The Journal of Steroid Biochemistry and Molecular Biology 94 (1–3): 203–8. February 2005. doi:10.1016/j.jsbmb.2005.01.007. PMID 15862967.
- "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research 14 (9): 1711–8. September 2004. doi:10.1101/gr.2435604. PMID 15342556.
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