PSTPIP2: Difference between revisions
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== Introduction == | |||
{{Infobox_gene}} | {{Infobox_gene}} | ||
'''Proline-serine-threonine phosphatase-interacting protein 2''' is an [[enzyme]] that in humans is encoded by the '' | '''Proline-serine-threonine phosphatase-interacting protein 2''' is an [[enzyme]] that in humans is encoded by the ''Pstpip2'' [[gene]].<ref name="pmid9804817">{{cite journal | vauthors = Wu Y, Dowbenko D, Lasky LA | title = PSTPIP 2, a second tyrosine phosphorylated, cytoskeletal-associated protein that binds a PEST-type protein-tyrosine phosphatase | journal = The Journal of Biological Chemistry | volume = 273 | issue = 46 | pages = 30487–96 | date = November 1998 | pmid = 9804817 | pmc = | doi = 10.1074/jbc.273.46.30487 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PSTPIP2 proline-serine-threonine phosphatase interacting protein 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9050| access-date = }}</ref> This protein, also known as macrophage F-actin-asosiated 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 <ref>{{cite journal | vauthors = Chitu V, Stanley ER | title = Pombe Cdc15 homology (PCH) proteins: coordinators of membrane-cytoskeletal interactions | journal = Trends in Cell Biology | volume = 17 | issue = 3 | pages = 145–56 | date = March 2007 | pmid = 17296299 | doi = 10.1016/j.tcb.2007.01.003 }}</ref> | ||
== | == Function == | ||
''Pstpip2'' is selectively expressed in [[macrophages]] and macrophage precursors<ref>{{cite journal | vauthors = Yeung YG, Soldera S, Stanley ER | title = A novel macrophage actin-associated protein (MAYP) is tyrosine-phosphorylated following colony stimulating factor-1 stimulation | journal = The Journal of Biological Chemistry | volume = 273 | issue = 46 | pages = 30638–42 | date = November 1998 | pmid = 9804836 }}</ref><ref name=":0">{{cite journal | vauthors = 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 | title = Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease | journal = Blood | volume = 107 | issue = 8 | pages = 3350–8 | date = April 2006 | pmid = 16397132 | pmc = 1895761 | doi = 10.1182/blood-2005-09-3556 | doi-access = free }}</ref>, and it is an [[actin]] bundling [[protein]] which regulates [[filopodia]] formation and [[macrophage]] motility<ref>{{cite journal | vauthors = Chitu V, Pixley FJ, Macaluso F, Larson DR, Condeelis J, Yeung YG, Stanley ER | title = The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages | journal = Molecular Biology of the Cell | volume = 16 | issue = 6 | pages = 2947–59 | date = June 2005 | pmid = 15788569 | pmc = 1142438 | doi = 10.1091/mbc.e04-10-0914 | doi-access = free }}</ref> | |||
== Cytokine expression profile == | |||
PSTPIP2 deficiency leads to elevated levels of circulating [[inflammatory mediators]] in vivo. In asymptomatic mice, only [[MIP-1α]] and [[Interleukin 6|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]]<<ref name="pmid19608749">{{cite journal | vauthors = Chitu V, Ferguson PJ, de Bruijn R, Schlueter AJ, Ochoa LA, Waldschmidt TJ, Yeung YG, Stanley ER | title = Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice | journal = Blood | volume = 114 | issue = 12 | pages = 2497–505 | date = September 2009 | pmid = 19608749 | pmc = 2746474 | doi = 10.1182/blood-2009-02-204925 }}</ref> and decreased levels of [[Interleukin 13|IL-13]]<ref name="pmid7903102">{{cite journal | vauthors = Doherty TM, Kastelein R, Menon S, Andrade S, Coffman RL | title = Modulation of murine macrophage function by IL-13 | journal = J. Immunol. | volume = 151 | issue = 12 | pages = 7151–60 | date = December 1993 | pmid = 7903102 }}</ref><ref name="pmid17981560">{{cite journal | vauthors = Martinez FO, Sica A, Mantovani A, Locati M | title = Macrophage activation and polarization | journal = Front. Biosci. | volume = 13 | issue = | pages = 453–61 | date = January 2008 | pmid = 17981560 }}</ref> | |||
< | == Disease linkage == | ||
{{ | The [[missense mutation]] I228N leads to a macrophage-mediated [[autoinflammatory disease]] called Lupo ''Pstpip2'' (Pstpip2<sup>Lupo/Lupo</sup> ). It is characterized by skin necrosis, inflammation of paws, ears and inflammatory bone resorption<ref name=":0" />. 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<ref>{{cite journal | vauthors = Chitu V, Ferguson PJ, de Bruijn R, Schlueter AJ, Ochoa LA, Waldschmidt TJ, Yeung YG, Stanley ER | title = Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice | journal = Blood | volume = 114 | issue = 12 | pages = 2497–505 | date = September 2009 | pmid = 19608749 | pmc = 2746474 | doi = 10.1182/blood-2009-02-204925 | doi-access = free }}</ref>. | ||
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==References== | == Interactions == | ||
PSTPIP2 interacts with protein tyrosine phosphatases from the proline-, glutamic acid-, serine- and threonine-rich (PEST) family <ref>{{cite journal | vauthors = Veillette A, Rhee I, Souza CM, Davidson D | title = PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders | journal = Immunological Reviews | volume = 228 | issue = 1 | pages = 312–24 | date = March 2009 | pmid = 19290936 | doi = 10.1111/j.1600-065x.2008.00747.x }}</ref>, SHIP1 and Csk<ref>{{cite journal | vauthors = Drobek A, Kralova J, Skopcova T, Kucova M, Novák P, Angelisová P, Otahal P, Alberich-Jorda M, Brdicka T | title = PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with Inhibitory Enzymes SHIP1 and Csk | journal = Journal of Immunology | volume = 195 | issue = 7 | pages = 3416–26 | date = October 2015 | pmid = 26304991 | doi = 10.4049/jimmunol.1401494 | doi-access = free }}</ref> | |||
== References == | |||
{{reflist}} | {{reflist}} | ||
==Further reading== | == Further reading == | ||
{{refbegin | 2}} | {{refbegin | 2}} | ||
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = January 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }} | |||
* {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }} | |||
*{{cite journal | * {{cite journal | vauthors = Pope SN, Lee IR | title = Yeast two-hybrid identification of prostatic proteins interacting with human sex hormone-binding globulin | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 94 | issue = 1-3 | pages = 203–8 | date = February 2005 | pmid = 15862967 | doi = 10.1016/j.jsbmb.2005.01.007 }} | ||
*{{cite journal | * {{cite journal | vauthors = Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S | title = Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions | journal = Genome Research | volume = 14 | issue = 9 | pages = 1711–8 | date = September 2004 | pmid = 15342556 | pmc = 515316 | doi = 10.1101/gr.2435604 }} | ||
*{{cite journal | |||
*{{cite journal | |||
{{refend}} | {{refend}} | ||
{{gene-18-stub}} | {{gene-18-stub}} | ||
Revision as of 19:36, 11 September 2018
Introduction
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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-asosiated 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 I228N 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
- ↑ 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.
- ↑ "Entrez Gene: PSTPIP2 proline-serine-threonine phosphatase interacting protein 2".
- ↑ 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.
- ↑ 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. PMID 9804836.
- ↑ 5.0 5.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 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. PMID 7903102.
- ↑ Martinez FO, Sica A, Mantovani A, Locati M (January 2008). "Macrophage activation and polarization". Front. Biosci. 13: 453–61. PMID 17981560.
- ↑ 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.
- ↑ 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.
- ↑ 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
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- Pope SN, Lee IR (February 2005). "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. doi:10.1016/j.jsbmb.2005.01.007. PMID 15862967.
- Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (September 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
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