Biology:Pleiotrophin
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Short description: Protein in humans
 Generic protein structure example |
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.[1] 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[2] and as a mitogen toward fibroblasts isolated from bovine uterus tissue.[3] Together with midkine these growth-factors constitute a family of (developmentally regulated) secreted heparin-binding proteins[4] 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.[5] Pleiotrophin is also expressed by several tumor cells and is thought to be involved in tumor angiogenesis.[6] In the adult central nervous system, pleiotrophin is expressed in an activity-dependent manner in the hippocampus[7][8] where it can suppress long term potentiation induction.[9] Pleiotrophin expression is low in other areas of the adult brain, but it can be induced by ischemic insults.[10][11] 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.[12]
References
- ↑ "Entrez Gene: PTN pleiotrophin (heparin binding growth factor 8, neurite growth-promoting factor 1)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5764.
- ↑ "Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons". J. Biol. Chem. 262 (34): 16625–35. 1987. doi:10.1016/S0021-9258(18)49302-7. PMID 3680268. http://www.jbc.org/cgi/content/abstract/262/34/16625.
- ↑ "Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity". Science 250 (4988): 1690–4. 1990. doi:10.1126/science.2270483. PMID 2270483. Bibcode: 1990Sci...250.1690L.
- ↑ "Biochemical and mitogenic properties of the heparin-binding growth factor HARP". Prog. Growth Factor Res. 6 (1): 25–34. 1995. doi:10.1016/0955-2235(95)00002-X. PMID 8714367.
- ↑ "Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues". Anat. Embryol. 186 (4): 387–406. 1992. doi:10.1007/BF00185989. PMID 1416088.
- ↑ "Midkine and pleiotrophin in neural development and cancer". Cancer Lett. 204 (2): 127–43. 2004. doi:10.1016/S0304-3835(03)00450-6. PMID 15013213.
- ↑ "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. 1993. doi:10.1016/0165-3806(93)90166-8. PMID 8453763.
- ↑ "Activity-induced enhancement of HB-GAM expression in rat hippocampal slices". NeuroReport 7 (10): 1670–4. 1996. doi:10.1097/00001756-199607080-00029. PMID 8904779.
- ↑ "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. 2002. doi:10.1006/mcne.2002.1104. PMID 12093164.
- ↑ "Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury". Neuroscience 68 (1): 57–64. 1995. doi:10.1016/0306-4522(95)00110-5. PMID 7477935.
- ↑ "Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury". J. Neurosci. 18 (10): 3699–707. 1998. doi:10.1523/JNEUROSCI.18-10-03699.1998. PMID 9570800.
- ↑ "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin". FEBS J. 272 (18): 4646–59. September 2005. doi:10.1111/j.1742-4658.2005.04870.x. PMID 16156786.
Further reading
- "Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene.". Biochemistry 31 (48): 12023–8. 1993. doi:10.1021/bi00163a009. PMID 1457401.
- "Characterization of the human pleiotrophin gene. Promoter region and chromosomal localization.". J. Biol. Chem. 267 (36): 26011–6. 1993. doi:10.1016/S0021-9258(18)35709-0. PMID 1464612.
- "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. 1991. doi:10.1016/S0006-291X(05)81048-4. PMID 1701634.
- "A heparin-binding growth factor secreted from breast cancer cells homologous to a developmentally regulated cytokine.". J. Biol. Chem. 267 (4): 2582–7. 1992. doi:10.1016/S0021-9258(18)45920-0. PMID 1733956.
- "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. 1992. doi:10.3109/08977199109000275. PMID 1768439.
- "Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity.". Science 250 (4988): 1690–4. 1991. doi:10.1126/science.2270483. PMID 2270483. Bibcode: 1990Sci...250.1690L.
- "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. 1990. doi:10.1007/BF00969930. PMID 2388713.
- "Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region.". J. Biol. Chem. 270 (44): 26404–10. 1995. doi:10.1074/jbc.270.44.26404. PMID 7592855.
- "Isolation of a neuronal cell surface receptor of heparin binding growth-associated molecule (HB-GAM). Identification as N-syndecan (syndecan-3).". J. Biol. Chem. 269 (17): 12999–3004. 1994. doi:10.1016/S0021-9258(18)99975-8. PMID 8175719.
- "Structural characterisation of native and recombinant forms of the neurotrophic cytokine MK.". J. Chromatogr. 646 (1): 213–25. 1993. doi:10.1016/S0021-9673(99)87023-X. PMID 8408430.
- "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. 1993. doi:10.1006/bbrc.1993.1432. PMID 8484754.
- "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. 1993. doi:10.1006/bbrc.1993.1476. PMID 8484780.
- "Neurite outgrowth in brain neurons induced by heparin-binding growth-associated molecule (HB-GAM) depends on the specific interaction of HB-GAM with heparan sulfate at the cell surface.". J. Biol. Chem. 271 (4): 2243–8. 1996. doi:10.1074/jbc.271.4.2243. PMID 8567685.
- "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. 1997. doi:10.1101/gr.6.9.791. PMID 8889548.
- "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. 1997. doi:10.1006/bbrc.1997.7188. PMID 9299545.
- "High affinity binding and overlapping localization of neurocan and phosphacan/protein-tyrosine phosphatase-zeta/beta with tenascin-R, amphoterin, and the heparin-binding growth-associated molecule.". J. Biol. Chem. 273 (12): 6998–7005. 1998. doi:10.1074/jbc.273.12.6998. PMID 9507007.
- "Regulation of mRNA localization by transmembrane signalling: local interaction of HB-GAM (heparin-binding growth-associated molecule) with the cell surface localizes beta-actin mRNA.". J. Cell Sci. 111 (20): 3073–80. 1998. doi:10.1242/jcs.111.20.3073. PMID 9739080.
- "Domain structure of pleiotrophin required for transformation.". J. Biol. Chem. 274 (19): 12959–62. 1999. doi:10.1074/jbc.274.19.12959. PMID 10224041.
- "Glycosaminoglycans promote HARP/PTN dimerization.". Biochem. Biophys. Res. Commun. 266 (2): 437–42. 2000. doi:10.1006/bbrc.1999.1835. PMID 10600521.
- "Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta.". Proc. Natl. Acad. Sci. U.S.A. 97 (6): 2603–8. 2000. doi:10.1073/pnas.020487997. PMID 10706604.
- "Efficient production of recombinant human pleio-trophin in yeast, Pichia pastoris.". Biosci. Biotechnol. Biochem. 67 (10): 2288–90. 2003. doi:10.1271/bbb.67.2288. PMID 14586125.
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