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 PTNgene.[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
peripheralnervous 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]
^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.
PMID1416088.
S2CID23579980.
^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.
PMID8453763.
^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.
PMID8904779.
^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.
PMID12093164.
S2CID24655036.
^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.
PMID7477935.
S2CID32945854.
Milner PG, Shah D, Veile R, et al. (1993). "Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene". Biochemistry. 31 (48): 12023–8.
doi:
10.1021/bi00163a009.
PMID1457401.
Tezuka K, Takeshita S, Hakeda Y, et al. (1991). "Isolation of mouse and human cDNA clones encoding a protein expressed specifically in osteoblasts and brain tissues". Biochem. Biophys. Res. Commun. 173 (1): 246–51.
doi:
10.1016/S0006-291X(05)81048-4.
PMID1701634.
Kretschmer PJ, Fairhurst JL, Decker MM, et al. (1992). "Cloning, characterization and developmental regulation of two members of a novel human gene family of neurite outgrowth-promoting proteins". Growth Factors. 5 (2): 99–114.
doi:
10.3109/08977199109000275.
PMID1768439.
Li YS, Milner PG, Chauhan AK, et al. (1991). "Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity". Science. 250 (4988): 1690–4.
Bibcode:
1990Sci...250.1690L.
doi:
10.1126/science.2270483.
PMID2270483.
Huber D, Gautschi-Sova P, Böhlen P (1990). "Amino-terminal sequences of a novel heparin-binding protein from human, bovine, rat, and chick brain: high interspecies homology". Neurochem. Res. 15 (4): 435–9.
doi:
10.1007/BF00969930.
PMID2388713.
S2CID24896178.
Fabri L, Maruta H, Muramatsu H, et al. (1993). "Structural characterisation of native and recombinant forms of the neurotrophic cytokine MK". J. Chromatogr. 646 (1): 213–25.
doi:
10.1016/S0021-9673(99)87023-X.
PMID8408430.
Kretschmer PJ, Fairhurst JL, Hulmes JD, et al. (1993). "Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant". Biochem. Biophys. Res. Commun. 192 (2): 420–9.
doi:
10.1006/bbrc.1993.1432.
PMID8484754.
Hulmes JD, Seddon AP, Decker MM, Böhlen P (1993). "Comparison of the disulfide bond arrangements of human recombinant and bovine brain heparin binding neurite-promoting factors". Biochem. Biophys. Res. Commun. 192 (2): 738–46.
doi:
10.1006/bbrc.1993.1476.
PMID8484780.
Masuda H, Tsujimura A, Yoshioka M, et al. (1997). "Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1". Biochem. Biophys. Res. Commun. 238 (2): 528–33.
doi:
10.1006/bbrc.1997.7188.
PMID9299545.
Murasugi A, Kido I, Kumai H, Asami Y (2003). "Efficient production of recombinant human pleio-trophin in yeast, Pichia pastoris". Biosci. Biotechnol. Biochem. 67 (10): 2288–90.
doi:
10.1271/bbb.67.2288.
PMID14586125.
S2CID23168994.
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 PTNgene.[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
peripheralnervous 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]
^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.
PMID1416088.
S2CID23579980.
^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.
PMID8453763.
^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.
PMID8904779.
^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.
PMID12093164.
S2CID24655036.
^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.
PMID7477935.
S2CID32945854.
Milner PG, Shah D, Veile R, et al. (1993). "Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene". Biochemistry. 31 (48): 12023–8.
doi:
10.1021/bi00163a009.
PMID1457401.
Tezuka K, Takeshita S, Hakeda Y, et al. (1991). "Isolation of mouse and human cDNA clones encoding a protein expressed specifically in osteoblasts and brain tissues". Biochem. Biophys. Res. Commun. 173 (1): 246–51.
doi:
10.1016/S0006-291X(05)81048-4.
PMID1701634.
Kretschmer PJ, Fairhurst JL, Decker MM, et al. (1992). "Cloning, characterization and developmental regulation of two members of a novel human gene family of neurite outgrowth-promoting proteins". Growth Factors. 5 (2): 99–114.
doi:
10.3109/08977199109000275.
PMID1768439.
Li YS, Milner PG, Chauhan AK, et al. (1991). "Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity". Science. 250 (4988): 1690–4.
Bibcode:
1990Sci...250.1690L.
doi:
10.1126/science.2270483.
PMID2270483.
Huber D, Gautschi-Sova P, Böhlen P (1990). "Amino-terminal sequences of a novel heparin-binding protein from human, bovine, rat, and chick brain: high interspecies homology". Neurochem. Res. 15 (4): 435–9.
doi:
10.1007/BF00969930.
PMID2388713.
S2CID24896178.
Fabri L, Maruta H, Muramatsu H, et al. (1993). "Structural characterisation of native and recombinant forms of the neurotrophic cytokine MK". J. Chromatogr. 646 (1): 213–25.
doi:
10.1016/S0021-9673(99)87023-X.
PMID8408430.
Kretschmer PJ, Fairhurst JL, Hulmes JD, et al. (1993). "Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant". Biochem. Biophys. Res. Commun. 192 (2): 420–9.
doi:
10.1006/bbrc.1993.1432.
PMID8484754.
Hulmes JD, Seddon AP, Decker MM, Böhlen P (1993). "Comparison of the disulfide bond arrangements of human recombinant and bovine brain heparin binding neurite-promoting factors". Biochem. Biophys. Res. Commun. 192 (2): 738–46.
doi:
10.1006/bbrc.1993.1476.
PMID8484780.
Masuda H, Tsujimura A, Yoshioka M, et al. (1997). "Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1". Biochem. Biophys. Res. Commun. 238 (2): 528–33.
doi:
10.1006/bbrc.1997.7188.
PMID9299545.
Murasugi A, Kido I, Kumai H, Asami Y (2003). "Efficient production of recombinant human pleio-trophin in yeast, Pichia pastoris". Biosci. Biotechnol. Biochem. 67 (10): 2288–90.
doi:
10.1271/bbb.67.2288.
PMID14586125.
S2CID23168994.