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== Function ==
== Function ==


Pleiotrophin was initially recognized as a neurite outgrowth-promoting factor present in rat brain around birth<ref name="pmid3680268">{{cite journal |vauthors=Rauvala H, Pihlaskari R | title = Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons | journal = J. Biol. Chem. | volume = 262 | issue = 34 | pages = 16625–35 | year = 1987 | pmid = 3680268 | doi = | issn = | url = http://www.jbc.org/cgi/content/abstract/262/34/16625 }}</ref> and as a mitogen toward fibroblasts isolated from bovine uterus tissue.<ref name="pmid2270483">{{cite journal |vauthors=Li YS, Milner PG, Chauhan AK, Watson MA, Hoffman RM, Kodner CM, Milbrandt J, Deuel TF | title = Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity | journal = Science | volume = 250 | issue = 4988 | pages = 1690–4 | year = 1990 | pmid = 2270483 | doi = 10.1126/science.2270483 }}</ref> Together with [[midkine]] these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins<ref name="pmid8714367">{{cite journal |vauthors=Laaroubi K, Vacherot F, Delbé J, Caruelle D, Barritault D, Courty J | title = Biochemical and mitogenic properties of the heparin-binding growth factor HARP | journal = Prog. Growth Factor Res. | volume = 6 | issue = 1 | pages = 25–34 | year = 1995 | pmid = 8714367 | doi = 10.1016/0955-2235(95)00002-X }}</ref> now known as the neurite growth-promoting factor (NEGF) family. During [[embryonal development|embryonic]] and early postnatal development, pleiotrophin is expressed in the [[central Nervous System|central]] and [[peripheral nervous system|peripheral]] [[nervous system]] and also in several non-neural [[biological tissue|tissues]], notably [[lung]], [[kidney]], [[Gut (zoology)|gut]] and [[bone]].<ref name="pmid1416088">{{cite journal |vauthors=Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ | title = Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues | journal = Anat. Embryol. | volume = 186 | issue = 4 | pages = 387–406 | year = 1992 | pmid = 1416088 | doi = 10.1007/BF00185989 }}</ref> Pleiotrophin is also expressed by several [[tumor]] cells and is thought to be involved in tumor [[angiogenesis]].<ref name="pmid15013213">{{cite journal |vauthors=Kadomatsu K, Muramatsu T | title = Midkine and pleiotrophin in neural development and cancer | journal = Cancer Lett. | volume = 204 | issue = 2 | pages = 127–43 | year = 2004 | pmid = 15013213 | doi = 10.1016/S0304-3835(03)00450-6 }}</ref> In the adult [[central nervous system]], pleiotrophin is expressed in an activity-dependent manner in the [[hippocampus]]<ref name="pmid8453763">{{cite journal |vauthors=Wanaka A, Carroll SL, Milbrandt J | title = Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat | journal = Brain Res. Dev. Brain Res. | volume = 72 | issue = 1 | pages = 133–44 | year = 1993 | pmid = 8453763 | doi = 10.1016/0165-3806(93)90166-8 }}</ref><ref name="pmid8904779">{{cite journal |vauthors=Lauri SE, Taira T, Kaila K, Rauvala H | title = Activity-induced enhancement of HB-GAM expression in rat hippocampal slices | journal = NeuroReport | volume = 7 | issue = 10 | pages = 1670–4 | year = 1996 | pmid = 8904779 | doi = 10.1097/00001756-199607080-00029 }}</ref> where it can suppress [[long term potentiation]] induction.<ref name="pmid12093164">{{cite journal |vauthors=Pavlov I, Võikar V, Kaksonen M, Lauri SE, Hienola A, Taira T, Rauvala H | title = Role of heparin-binding growth-associated molecule (HB-GAM) in hippocampal LTP and spatial learning revealed by studies on overexpressing and knockout mice | journal = Mol. Cell. Neurosci. | volume = 20 | issue = 2 | pages = 330–42 | year = 2002 | pmid = 12093164 | doi = 10.1006/mcne.2002.1104 }}</ref> Pleiotrophin expression is low in other areas of the adult [[brain]], but it can be induced by [[ischemic]] insults.<ref name="pmid7477935">{{cite journal |vauthors=Takeda A, Onodera H, Sugimoto A, Itoyama Y, Kogure K, Rauvala H, Shibahara S | title = Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury | journal = Neuroscience | volume = 68 | issue = 1 | pages = 57–64 | year = 1995 | pmid = 7477935 | doi = 10.1016/0306-4522(95)00110-5 }}</ref><ref name="pmid9570800">{{cite journal |vauthors=Yeh HJ, He YY, Xu J, Hsu CY, Deuel TF | title = Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury | journal = J. Neurosci. | volume = 18 | issue = 10 | pages = 3699–707 | year = 1998 | pmid = 9570800 | doi = | issn = | url = http://www.jneurosci.org/cgi/content/abstract/18/10/3699 }}</ref> or targeted neuronal damaged in the [[entorhinal cortex]] or in the [[Substantia nigra pars compacta#Pars Compacta 2|substantia nigra pars compacta]].
Pleiotrophin was initially recognized as a neurite outgrowth-promoting factor present in rat brain around birth<ref name="pmid3680268">{{cite journal |vauthors=Rauvala H, Pihlaskari R | title = Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons | journal = J. Biol. Chem. | volume = 262 | issue = 34 | pages = 16625–35 | year = 1987 | pmid = 3680268 | doi = | issn = | url = http://www.jbc.org/cgi/content/abstract/262/34/16625 }}</ref> and as a mitogen toward fibroblasts isolated from bovine uterus tissue.<ref name="pmid2270483">{{cite journal |vauthors=Li YS, Milner PG, Chauhan AK, Watson MA, Hoffman RM, Kodner CM, Milbrandt J, Deuel TF | title = Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity | journal = Science | volume = 250 | issue = 4988 | pages = 1690–4 | year = 1990 | pmid = 2270483 | doi = 10.1126/science.2270483 }}</ref> Together with [[midkine]] these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins<ref name="pmid8714367">{{cite journal |vauthors=Laaroubi K, Vacherot F, Delbé J, Caruelle D, Barritault D, Courty J | title = Biochemical and mitogenic properties of the heparin-binding growth factor HARP | journal = Prog. Growth Factor Res. | volume = 6 | issue = 1 | pages = 25–34 | year = 1995 | pmid = 8714367 | doi = 10.1016/0955-2235(95)00002-X }}</ref> now known as the neurite growth-promoting factor (NEGF) family. During [[embryonal development|embryonic]] and early postnatal development, pleiotrophin is expressed in the [[central Nervous System|central]] and [[peripheral nervous system|peripheral]] [[nervous system]] and also in several non-neural [[biological tissue|tissues]], notably [[lung]], [[kidney]], [[Gut (zoology)|gut]] and [[bone]].<ref name="pmid1416088">{{cite journal |vauthors=Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ | title = Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues | journal = Anat. Embryol. | volume = 186 | issue = 4 | pages = 387–406 | year = 1992 | pmid = 1416088 | doi = 10.1007/BF00185989 }}</ref> Pleiotrophin is also expressed by several [[tumor]] cells and is thought to be involved in tumor [[angiogenesis]].<ref name="pmid15013213">{{cite journal |vauthors=Kadomatsu K, Muramatsu T | title = Midkine and pleiotrophin in neural development and cancer | journal = Cancer Lett. | volume = 204 | issue = 2 | pages = 127–43 | year = 2004 | pmid = 15013213 | doi = 10.1016/S0304-3835(03)00450-6 }}</ref> In the adult [[central nervous system]], pleiotrophin is expressed in an activity-dependent manner in the [[hippocampus]]<ref name="pmid8453763">{{cite journal |vauthors=Wanaka A, Carroll SL, Milbrandt J | title = Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat | journal = Brain Res. Dev. Brain Res. | volume = 72 | issue = 1 | pages = 133–44 | year = 1993 | pmid = 8453763 | doi = 10.1016/0165-3806(93)90166-8 }}</ref><ref name="pmid8904779">{{cite journal |vauthors=Lauri SE, Taira T, Kaila K, Rauvala H | title = Activity-induced enhancement of HB-GAM expression in rat hippocampal slices | journal = NeuroReport | volume = 7 | issue = 10 | pages = 1670–4 | year = 1996 | pmid = 8904779 | doi = 10.1097/00001756-199607080-00029 }}</ref> where it can suppress [[long term potentiation]] induction.<ref name="pmid12093164">{{cite journal |vauthors=Pavlov I, Võikar V, Kaksonen M, Lauri SE, Hienola A, Taira T, Rauvala H | title = Role of heparin-binding growth-associated molecule (HB-GAM) in hippocampal LTP and spatial learning revealed by studies on overexpressing and knockout mice | journal = Mol. Cell. Neurosci. | volume = 20 | issue = 2 | pages = 330–42 | year = 2002 | pmid = 12093164 | doi = 10.1006/mcne.2002.1104 }}</ref> Pleiotrophin expression is low in other areas of the adult [[brain]], but it can be induced by [[ischemic]] insults.<ref name="pmid7477935">{{cite journal |vauthors=Takeda A, Onodera H, Sugimoto A, Itoyama Y, Kogure K, Rauvala H, Shibahara S | title = Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury | journal = Neuroscience | volume = 68 | issue = 1 | pages = 57–64 | year = 1995 | pmid = 7477935 | doi = 10.1016/0306-4522(95)00110-5 }}</ref><ref name="pmid9570800">{{cite journal |vauthors=Yeh HJ, He YY, Xu J, Hsu CY, Deuel TF | title = Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury | journal = J. Neurosci. | volume = 18 | issue = 10 | pages = 3699–707 | year = 1998 | pmid = 9570800 | doi = | issn = | url = http://www.jneurosci.org/cgi/content/abstract/18/10/3699 | pmc = 6793139 }}</ref> or targeted neuronal damaged in the [[entorhinal cortex]] or in the [[Substantia nigra pars compacta#Pars Compacta 2|substantia nigra pars compacta]].


== Clinical significance ==
== Clinical significance ==

Revision as of 13:33, 27 July 2020

PTN
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPTN, HARP, HBGF8, HBNF, NEGF1, HB-GAM, HBBM, HBGF-8, HBNF-1, OSF-1, pleiotrophin
External IDsOMIM: 162095; MGI: 97804; HomoloGene: 2117; GeneCards: PTN; OMA:PTN - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002825
NM_001321386
NM_001321387

NM_008973

RefSeq (protein)

NP_001308315
NP_001308316
NP_002816

NP_032999

Location (UCSC)Chr 7: 137.23 – 137.34 MbChr 6: 36.69 – 36.79 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Pleiotrophin (PTN) also known as heparin-binding brain mitogen (HBBM) or heparin-binding growth factor 8 (HBGF-8) or neurite growth-promoting factor 1 (NEGF1) or heparin affinity regulatory peptide (HARP) or heparin binding growth associated molecule (HB-GAM) is a protein that in humans is encoded by the PTN gene.[5] Pleiotrophin is an 18-kDa growth factor that has a high affinity for heparin. It is structurally related to midkine and retinoic acid induced heparin-binding protein.

Function

Pleiotrophin was initially recognized as a neurite outgrowth-promoting factor present in rat brain around birth[6] and as a mitogen toward fibroblasts isolated from bovine uterus tissue.[7] Together with midkine these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins[8] now known as the neurite growth-promoting factor (NEGF) family. During embryonic and early postnatal development, pleiotrophin is expressed in the central and peripheral nervous system and also in several non-neural tissues, notably lung, kidney, gut and bone.[9] Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis.[10] In the adult central nervous system, pleiotrophin is expressed in an activity-dependent manner in the hippocampus[11][12] where it can suppress long term potentiation induction.[13] Pleiotrophin expression is low in other areas of the adult brain, but it can be induced by ischemic insults.[14][15] or targeted neuronal damaged in the entorhinal cortex or in the substantia nigra pars compacta.

Clinical significance

Pleiotrophin binds to cell-surface nucleolin as a low affinity receptor. This binding can inhibit HIV infection.[16]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000105894Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029838Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: PTN pleiotrophin (heparin binding growth factor 8, neurite growth-promoting factor 1)".
  6. ^ Rauvala H, Pihlaskari R (1987). "Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons". J. Biol. Chem. 262 (34): 16625–35. PMID 3680268.
  7. ^ Li YS, Milner PG, Chauhan AK, Watson MA, Hoffman RM, Kodner CM, Milbrandt J, Deuel TF (1990). "Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity". Science. 250 (4988): 1690–4. doi:10.1126/science.2270483. PMID 2270483.
  8. ^ Laaroubi K, Vacherot F, Delbé J, Caruelle D, Barritault D, Courty J (1995). "Biochemical and mitogenic properties of the heparin-binding growth factor HARP". Prog. Growth Factor Res. 6 (1): 25–34. doi:10.1016/0955-2235(95)00002-X. PMID 8714367.
  9. ^ Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ (1992). "Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues". Anat. Embryol. 186 (4): 387–406. doi:10.1007/BF00185989. PMID 1416088.
  10. ^ Kadomatsu K, Muramatsu T (2004). "Midkine and pleiotrophin in neural development and cancer". Cancer Lett. 204 (2): 127–43. doi:10.1016/S0304-3835(03)00450-6. PMID 15013213.
  11. ^ Wanaka A, Carroll SL, Milbrandt J (1993). "Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat". Brain Res. Dev. Brain Res. 72 (1): 133–44. doi:10.1016/0165-3806(93)90166-8. PMID 8453763.
  12. ^ Lauri SE, Taira T, Kaila K, Rauvala H (1996). "Activity-induced enhancement of HB-GAM expression in rat hippocampal slices". NeuroReport. 7 (10): 1670–4. doi:10.1097/00001756-199607080-00029. PMID 8904779.
  13. ^ Pavlov I, Võikar V, Kaksonen M, Lauri SE, Hienola A, Taira T, Rauvala H (2002). "Role of heparin-binding growth-associated molecule (HB-GAM) in hippocampal LTP and spatial learning revealed by studies on overexpressing and knockout mice". Mol. Cell. Neurosci. 20 (2): 330–42. doi:10.1006/mcne.2002.1104. PMID 12093164.
  14. ^ Takeda A, Onodera H, Sugimoto A, Itoyama Y, Kogure K, Rauvala H, Shibahara S (1995). "Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury". Neuroscience. 68 (1): 57–64. doi:10.1016/0306-4522(95)00110-5. PMID 7477935.
  15. ^ Yeh HJ, He YY, Xu J, Hsu CY, Deuel TF (1998). "Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury". J. Neurosci. 18 (10): 3699–707. PMC 6793139. PMID 9570800.
  16. ^ Said EA, Courty J, Svab J, Delbé J, Krust B, Hovanessian AG (September 2005). "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin". FEBS J. 272 (18): 4646–59. doi:10.1111/j.1742-4658.2005.04870.x. PMID 16156786.

Further reading