THYMOSIN BETA 4 From wikipedia... http://en.wikipedia.org/wiki/Beta_thymosins Beta thymosins are a family of proteins which have in common a sequence of about 40 amino acids similar to the small protein thymosinβ4. They are found almost exclusively in multicellular animals. Thymosin β4 was originally obtained from the thymus in company with several other small proteins which although named collectively "thymosins" are now known to be structurally and genetically unrelated and present in many different animal tissues.
Monomericβ-thymosins, i.e. those of molecular weight similar to those originally isolated from thymus by Goldstein, are found almost exclusively in cells of multicellular animals.[4]Although found even in very early diverged animals such as sponges, monomeric thymosins are absent from arthropods and nematodes, which do nevertheless possess proteins, known as β-thymosin repeat proteins, which are constructed from several end-to-end repeats of β-thymosin sequences.[5]Genomics has shown that tetrapods(land vertebrates) each express three monomeric β-thymosins, which are the animal species' equivalents (orthologues) of human β4, β10and β15 thymosins, respectively. The human thymosins are encoded by the genes TMSB4X, TMSB10 and TMSB15A and TMSB15B. Bony fishin general express orthologues of these same three, plus an additional copy of the β4 orthologue.[6]
Relation to the WH2 sequence module The N-terminal half of β-thymosins bears a strong similarity in amino acid sequence to a very widely distributed sequence module, the WH2module. (Wasp Homology Domain 2 - the name is derived from Wiskott-Aldrich syndrome protein).[7][8]Evidence from X-ray crystallography shows that this part ofβ-thymosins binds to actinin a near-identical manner to that of WH2 modules, both adopting as they bind, a conformation which has been referred to as the β-thymosin/WH2fold. β-thymosins may therefore have evolved by addition of novel C-terminal sequence to an ancestral WH2 module.[9]However, sequence similarity searches designed to identify present-day WH2 domains[10]fail to recognise β-thymosins, (and vice versa) and the sequence and functional similarities may result from convergent evolution.[11] Biological activities of thymosin β4 The archetypical β-thymosin is β4 (product in humans of the TMSB4Xgene), which is a major cellular constituent in many tissues. Its intracellular concentration may reach as high as 0.5 mM.[12]Following Thymosin α1, β4 was the second of the biologically active peptides from Thymosin Fraction 5 to be completely sequenced and synthesized.[13] Actin binding Thymosin β4was initially perceived as a thymic hormone. However this changed when it was discovered that it forms a 1:1 complex with G (globular) actin, and is present at high concentration in a wide range of mammalian cell types.[14]When appropriate, G-actin monomers polymerize to form F (filamentous) actin which together with other proteins that bind to actin comprise cellular microfilaments. Formation by G-actin of the complex with β-thymosin (= "sequestration") opposes this.
Due to its profusion in the cytosoland its ability to bind G-actin but not F-actin, thymosin β4 is regarded as the principal actin-sequestering protein. Thymosin β4 functions like a buffer for monomeric actin as represented in the following reaction:[15] F-actin ↔ G-actin + Thymosin β4 ↔ G-actin/Thymosin β4
Release of G-actin monomers from thymosin β4 occurs as part of the mechanism that drives actin polymerization in the normal function of the cytoskeletonin cell morphology and cell motility. "Moonlighting" In addition to its intracellular role as the major actin-sequestering molecule in cells of many multicellular animals, thymosin β4 shows a remarkably diverse range of effects when present in the fluid surrounding animal tissue cells. Taken together, these effects suggest that thymosin has a general role in tissue regeneration. This has suggested a variety of possible therapeutic applications, and several have now been extended to animal models and human clinical trials.
It is considered unlikely that thymosin β4 exerts all these effects via intracellular sequestration of G-actin. This would require its uptake by cells, and moreover, in most cases the cells affected already have substantial intracellular concentrations. The diverse activities related to tissue repair may depend on interactions with receptors quite distinct from actin and possessing extracellular ligand-binding domains. Such multi-tasking by, or "partner promiscuity" of, proteins has been referred to as protein moonlighting.[16]Proteins such as thymosins which lack stable folded structure in aqueous solution, are known as intrinsically unstructured proteins(IUPs). Because IUPs acquire specific folded structures only on binding to their partner proteins, they offer special possibilities for interaction with multiple partners.[17]A candidate extracellular receptor of high affinity for thymosin β4is the β subunit of cell surface-located ATP synthase, which would allow extracellular thymosin to signal via a purinergic receptor.[18]
Some of the multiple activities of thymosin β4 unrelated to actin may be mediated by a tetrapeptide enzymically-cleaved from its N-terminus, N-acetyl-ser-asp-lys-pro, brand names Seraspenide or Goralatide, best known as an inhibitor of the proliferation of haematopoietic(blood-cell precursor) stem cells of bone marrow. Tissue regeneration Work with cell cultures and experiments with animals have shown that administration of thymosin β4 can promote migration of cells, formation of blood vessels, maturation of stem cells, survival of various cell types and lowering of the production of pro-inflammatory cytokines. These multiple properties have provided the impetus for a world-wide series of on-going clinical trials of potential effectiveness of thymosin β4 in promoting repair of wounds in skin, cornea and heart.[19]
Such tissue-regenerating properties of thymosin β4 may ultimately contribute to repair of human heart muscle damaged by heart disease and heart attack. In mice, administration of thymosin β4 has been shown to stimulate formation of new heart muscle cells from otherwise inactive precursor cells present in the outer lining of adult hearts,[20]to induce migration of these cells into heart muscle[21]and recruit new blood vessels within the muscle.[22] Anti-inflammatory role for sulfoxide In 1999 researchers in Glasgow University found that an oxidised derivative of thymosinβ4 (the sulfoxide, in which an oxygen atom is added to the methioninenear the N-terminus) exerted several potentially anti-inflammatoryeffects on neutrophilleucocytes. It promoted their dispersion from a focus, inhibited their response to a small peptide (F-Met-Leu-Phe) which attracts them to sites of bacterial infection and lowered their adhesion to endothelialcells. (Adhesion to endothelial cells of blood vessel walls is pre-requisite for these cells to leave the bloodstream and invade infected tissue). A possible anti-inflammatory role for the β4 sulfoxide was supported by the group's finding that it counteracted artificially-induced inflammation in mice.
The group had first identified the thymosin sulfoxide as an active factor in culture fluid of cells responding to treatment with a steroid hormone, suggesting that its formation might form part of the mechanism by which steroids exert anti-inflammatory effects. Extracellular thymosin β4would be readily oxidised to the sulfoxide in vivo at sites of inflammation, by the respiratory burst.[23] Terminal deoxynucleotidyl transferase Thymosin β4induces the activity of the enzyme terminal deoxynucleotidyl transferase in populations of thymocytes(thymus-derived lymphocytes). This suggests that the peptide may contribute to the maturation of these cells.[13] Clinical applications Thymosin β4is currently in multicenter trials in the United States and Europe in patients with bed sores, ulcers caused by venostasis, and Epidermolysis bullosa simplex. It is also about to enter clinical trials in diabetic patients who have been subjected to vitrectomy and in patients who have experienced heart attacks (myocardial infarction). Levels of human thymosin β15 in urine have shown promise as a diagnostic marker for prostate cancer which is sensitive to potential aggressivenes of the tumour [24] β-thymosin repeat proteins These proteins, which typically contain 2-4 repeats of the β-thymosin sequence, are chiefly found within lower metazoan species such as dipteran flies and nematodes.[25]The one mammalian exception, a dimer in mouse, is synthesised by transcriptional read-through between two copies of the mouse β15 gene, each of which is also transcribed separately.[26]A uniquely multiple example is the protein thypedin of Hydra which has 27 repeats of a β-thymosin sequence.[27] Biological activities β-thymosin repeat proteins resemble the monomeric forms in being able to bind to actin, but sequence differences in a studied example, the three-repeat protein Ciboulotof the fruit fly Drosophila, allow binding to ends of actin filaments, an activity which differs from monomer sequestration.[28]
These proteins became of interest in neurobiology with the finding that in the nudibranch (sea slug) Hermissenda crassicornis, the protein Csp24 (conditioned stimulus pathway phosphoprotein-24), with 4 repeats, is involved in one-trial enhancement of the excitability of sensory neurons in the conditioned stimulus pathway, a simple form of learning.[29] References 1. ^ Grottesi A, Sette M, Palamara T, Rotilio G, Garaci E, Paci M (1998). "The conformation of peptide thymosin alpha 1 in solution and in a membrane-like environment by circular dichroism and NMR spectroscopy. A possible model for its interaction with the lymphocyte membrane". Peptides 19 (10): 1731–8. PMID 9880079. 2. ^ a b PDB 1HJ0; Stoll R, Voelter W, Holak TA (May 1997). "Conformation of thymosin beta 9 in water/fluoroalcohol solution determined by NMR spectroscopy". Biopolymers 41 (6): 623–34. doi:10.1002/(SICI)1097-0282(199705)41:6<623::AID-BIP3>3.0.CO;2-S. PMID 9108730. "The thymosin is β9, bovine orthologue of human β10. Stabilised by organic solvent, the structure was determined by NMR. (Free β-thymosins lack a stable fold in solution)". 3. ^ Stoll R, Voelter W, Holak TA (May 1997). "Conformation of thymosin beta 9 in water/fluoroalcohol solution determined by NMR spectroscopy". Biopolymers 41 (6): 623–34. doi:10.1002/(SICI)1097-0282(199705)41:6<623::AID-BIP3>3.0.CO;2-S. PMID 9108730. 4. ^ "Family: Thymosin (PF01290)". Pfam. Wellcome Trust Sanger Institute. http://pfam.sanger.ac.uk/family?acc=PF01290#tabview=tab1. 5. ^ Manuel M, Kruse M, Müller WE, Le Parco Y (October 2000). "The comparison of beta-thymosin homologues among metazoa supports an arthropod-nematode clade". J. Mol. Evol. 51 (4): 378–81. doi:10.1007/s002390010100. PMID 11040289. 6. ^ Edwards J (March 2010). "Vertebrate beta-thymosins: conserved synteny reveals the relationship between those of bony fish and of land vertebrates". FEBS Lett. 584 (5): 1047–53. doi:10.1016/j.febslet.2010.02.004. PMID 20138884. 7. ^ Paunola E, Mattila PK, Lappalainen P (February 2002). "WH2 domain: a small, versatile adapter for actin monomers". FEBS Lett. 513 (1): 92–7. PMID 11911886. 8. ^ "Family: WH2 (PF02205)". Pfam. Wellcome Trust Sanger Institute. http://pfam.sanger.ac.uk/family?acc=PF02205#tabview=tab6. 9. ^ Dominguez R (September 2007). "The beta-thymosin/WH2 fold: multifunctionality and structure". Ann. N. Y. Acad. Sci. 1112: 86–94. doi:10.1196/annals.1415.011. PMID 17468236. 10. ^ "Family: WH2 (PF02205)". Pfam. Wellcome Trust Sanger Institute. http://pfam.sanger.ac.uk/family?acc=PF02205#tabview=tab2. 11. ^ Edwards J (August 2004). "Are beta-thymosins WH2 domains?". FEBS Lett. 573 (1–3): 231–2; author reply 233. doi:10.1016/j.febslet.2004.07.038. PMID 15328003. 12. ^ Hannappel E (September 2007). "beta-Thymosins". Ann. N. Y. Acad. Sci. 1112: 21–37. doi:10.1196/annals.1415.018. PMID 17468232. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2007&volume=1112&spage=21. 13. ^ a b Low TL, Hu SK, Goldstein AL (February 1981). "Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations". Proc. Natl. Acad. Sci. U.S.A. 78 (2): 1162–6. PMC 319967. PMID 6940133. 14. ^ Safer D, Elzinga M, Nachmias VT (March 1991). "Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable". J. Biol. Chem. 266 (7): 4029–32. PMID 1999398. 15. ^ Lodish, Harvey F. (2000). "Chapter 18. Cell Motility and Shape I: Microfilaments. 18.2. The Dynamics of Actin Assembly". Molecular cell biology. San Francisco: W.H. Freeman. ISBN 0-7167-3706-X. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.section.5145. 16. ^ Jeffery CJ (January 1999). "Moonlighting proteins". Trends Biochem. Sci. 24 (1): 8–11. PMID 10087914. 17. ^ Tompa P, Szász C, Buday L (September 2005). "Structural disorder throws new light on moonlighting". Trends Biochem. Sci. 30 (9): 484–9. doi:10.1016/j.tibs.2005.07.008. PMID 16054818. 18. ^ Freeman KW, Bowman BR, Zetter BR (November 2010). "Regenerative protein thymosin {beta}-4 is a novel regulator of purinergic signaling". FASEB J. doi:10.1096/fj.10-169417. PMID 21106936. 19. ^ Philp D, Kleinman HK (April 2010). "Animal studies with thymosin beta, a multifunctional tissue repair and regeneration peptide". Ann. N. Y. Acad. Sci. 1194: 81–6. doi:10.1111/j.1749-6632.2010.05479.x. PMID 20536453. 20. ^ Smart N, Bollini D, Dubé KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR (June 2011). "De novo cardiomyocytes from within the activated adult heart after injury". Nature 474. doi:10.1038/nature10188. PMID 21654746. Lay summary – BBC News. 21. ^ Smart N, Riley PR (February 2009). "Derivation of epicardium-derived progenitor cells (EPDCs) from adult epicardium". Curr Protoc Stem Cell Biol Chapter 2: Unit2C.2. doi:10.1002/9780470151808.sc02c02s8. PMID 19235142. 22. ^ Riley PR, Smart N (December 2009). "Thymosin beta4 induces epicardium-derived neovascularization in the adult heart". Biochem. Soc. Trans. 37 (Pt 6): 1218–20. doi:10.1042/BST0371218. PMID 19909250. 23. ^ Young JD, Lawrence AJ, MacLean AG, et al. (December 1999). "Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids". Nat. Med. 5 (12): 1424–7. doi:10.1038/71002. PMID 10581087. . 24. ^ Hutchinson LM, Chang EL, Becker CM, et al. (July 2005). "Use of thymosin beta15 as a urinary biomarker in human prostate cancer". Prostate 64 (2): 116–27. doi:10.1002/pros.20202. PMID 15666387. 25. ^ Pekka Lappalainen (2007). Actin-Monomer-Binding Proteins. Boston, MA: Landes Bioscience and Springer Science+Business Media, LLC. ISBN 0-387-46407-7. 26. ^ Dhaese S, Vandepoele K, Waterschoot D, Vanloo B, Vandekerckhove J, Ampe C, Van Troys M (April 2009). "The mouse thymosin beta15 gene family displays unique complexity and encodes a functional thymosin repeat". J. Mol. Biol. 387 (4): 809–25. doi:10.1016/j.jmb.2009.02.026. PMID 19233202. 27. ^ Herrmann D, Hatta M, Hoffmeister-Ullerich SA (November 2005). "Thypedin, the multi copy precursor for the hydra peptide pedin, is a beta-thymosin repeat-like domain containing protein". Mech. Dev. 122 (11): 1183–93. doi:10.1016/j.mod.2005.07.003. PMID 16169708. 28. ^ Carlier MF, Hertzog M, Didry D, Renault L, Cantrelle FX, van Heijenoort C, Knossow M, Guittet E (September 2007). "Structure, function, and evolution of the beta-thymosin/WH2 (WASP-Homology2) actin-binding module". Ann. N. Y. Acad. Sci. 1112: 67–75. doi:10.1196/annals.1415.037. PMID 17947587. 29. ^ Redell JB, Xue-Bian JJ, Bubb MR, Crow T (August 2007). "One-trial in vitro conditioning regulates an association between the beta-thymosin repeat protein Csp24 and actin". Neuroscience 148 (2): 413–20. doi:10.1016/j.neuroscience.2007.06.023. PMID 17681698.
MORE ON THYMOSINS From wikipedia... http://en.wikipedia.org/wiki/Thymosins
Thymosins are small polypeptides present in animal tissues. They are named thymosins because they were originally isolated from the thymus, but most are now known to be present in many other tissues. Thymosins have diverse biological activities, and two in particular, thymosins α1 and β4, have potentially important uses in medicine, some of which have already progressed from the laboratory to the clinic. In relation to diseases, thymosins have been categorized as biological response modifiers. Discovery
The discovery of thymosins in the mid 1960s emerged from investigations of the role of the thymus in development of the vertebrate immune system. Begun by Allan Goldstein in the Laboratory of Abraham White at the Albert Einstein College of Medicine in New York, the work continued at University of Texas Medical Branch in Galveston and at The George Washington University School of Medicine and Health Sciences in Washington D.C. The supposition that the role of the thymus might involve a hormone-like mechanism led to the isolation from thymus tissue of a biologically active preparation. Known as "Thymosin Fraction 5", this was able to restore some aspects of immune function in animals lacking thymus gland. Fraction 5 was found to contain a number of small peptides, which were named "thymosins" and classified as α, β and γ thymosins on the basis of their behaviour in an electric field. When individual thymosins were isolated from Fraction 5 and characterized, they were found to have extremely varied and important biological properties. However they are not truly thymic hormones in that they are not restricted in occurrence to thymus and several are widely distributed throughout many different tissues. [3][4][5]
Thymosin α1
Thymosin α1 is believed to be a major component of Thymosin Fraction 5 responsible for the activity of that preparation in restoring immune function in animals lacking thymus glands. It was the first of the peptides from Thymosin Fraction 5 to be completely sequenced and synthesized. Unlike β thymosins, to which it is genetically and chemically unrelated, thymosin α1 is produced as a 28-amino acid fragment, from a longer, 113-amino acid precursor, prothymosin α.[6] It has been found to enhance cell-mediated immunity in humans as well as experimental animals.[7] Thymosin α1 is now approved in 35 countries for the treatment of Hepatitis B and C, It is also approved for inclusion with vaccines to boost the immune response in the treatment of other diseases. [8] [9] Single domain β-thymosins
Monomeric β-thymosins, i.e. those of molecular weight similar to those originally isolated by Goldstein, are found only in cells of multicellular animals.[10] They are absent from many invertebrates, which do nevertheless possess proteins, known as β-thymosin repeat proteins, which are constructed from several end-to-end repeats of β-thymosin sequences. Genomics has shown that tetrapods (land vertebrates) each express three β-thymosins, which are the species equivalents (orthologues) of human β4, β10 and β15 thymosins respectively. Bony fish in general express orthologues of these same three, plus an additional copy of the β4 orthologue.[11]
Relation to the WH2 sequence module The N-terminal half of β-thymosins bears a strong similarity in amino acid sequence to a very widely distributed sequence module, the WH2 (Wasp Homology 2) domain.[12][13] Evidence from X-ray crystallography shows that this part of β-thymosins binds to actin in a near-identical manner to that of WH2 modules, both adopting as they bind, a conformation which has been referred to as the β-thymosin/WH2 fold. β-thymosins may therefore have evolved by addition of novel C-terminal sequence to an ancestral WH2 module.[14] However, sequence similarity searches designed to identify present-day WH2 domains[15] fail to recognise β-thymosins, and the sequence and functional similarities may result from convergent evolution.[16] Biological activities The archetypical β-thymosin is β4, which is a major cellular constituent in many tissues. Its intracellular concentration may reach as high as 0.5 mM.[4] Following Thymosin α1, β4 was the second of the biologically active peptides from Thymosin Fraction 5 to be completely sequenced and synthesized.[17]. In addition to its role as the major actin-sequestering molecule in cells of most multicellular animals, β4 thymosin shows a remarkable range of effects when added to the medium surrounding cells in culture. Taken together, they suggest that thymosin has a general role in tissue repair. These effects have suggested a range of possible therapeutic applications, and several have been extended to animal models and human clinical trials. It is considered unlikely that β4 thymosin exerts all these effects via intracellular sequestration of G-actin. This would require its uptake by cells, and moreover, in most cases the cells affected already have substantial intracellular concentrations. It is possible that the diverse activities related to tissue repair may depend on interactions with intra- or extracellular receptors quite distinct from actin and possibly including receptors with extracellular recognition domains. Such multi-tasking by, or "partner promiscuity" of proteins has been referred to as "moonlighting" [18]. Proteins such as thymosins lack stable folded structure in aqueous solution, and are examples of intrinsically unstructured proteins (IUPs). Because IUPs acquire specific folded structures on binding to their partner proteins, they offer special possibilities for interaction with multiple partners [19].
It was initially thought that thymosin β4 was solely a thymic hormone. However this perception changed when it was discovered that it forms a 1:1 complex with G (globular) actin, and is present at high concentration in a wide range of mammalian cell types.[20] When appropriate, G-actin monomers polymerize to form F (filamentous) actin which together with other proteins that bind to actin comprise cellular microfilaments. Formation by G-actin of the complex with β-thymosin (= "sequestration") opposes this. Due to its profusion in the cytosol and its ability to bind G-actin but not F-actin, thymosin β4 is regarded as the principal actin-sequestering protein. Thymosin β4 functions like a buffer for monomeric actin as represented in the following reaction:[21] F-actin ↔ G-actin + Thymosin β4 ↔ G-actin/Thymosin β4 Release of G-actin monomers from thymosin β4 occurs as part of the mechanism that drives rapid actin polymerization in the normal function of the cytoskeleton in cell morphology and cell motility. Terminal deoxynucleotidyl transferase Thymosin β4 induces the activity of the enzyme terminal deoxynucleotidyl transferase in populations of thymocytes (thymus-derived lymphocytes). This suggests that the peptide may contribute to the maturation of these cells.[22]. Clinical applications Thymosin β4 is currently in multicenter trials in the United States and Europe in patients with bed sores, ulcers caused by venostasis , and Epidermolysis bullosa simplex. It is also about to enter clinical trials in diabetic patients who have been subjected to vitrectomy and in patients who have experienced heart attacks (myocardial infarction). β-thymosin repeat proteins Distribution These proteins, which typically contain 2-4 repeats of the β-thymosin sequence, are chiefly found within lower metazoan species such as dipteran flies and nematodes [23]. The one mammalian exception, a dimer in mouse, is synthesised by transcriptional read-through between two copies of the mouse β15 gene, each of which is also transcribed separately [24]. A uniquely multiple example is the protein thypedin of Hydra which has 27 repeats of the β-thymosin sequence [25]. Biological activities β-thymosin repeat proteins resemble the monomeric forms in being able to bind to actin, but sequence differences in a studied example, the three-repeat protein Ciboulot of the fruit fly Drosophila, allow binding to ends of actin filaments, an activity which differs from monomer sequestration [26]. These proteins became of interest in neurobiology with the finding that in the nudibranch (sea slug) Hermissenda crassicornis, the protein Csp24 (conditioned stimulus pathway phosphoprotein-24), with 4 repeats, is involved in one-trial enhancement of the excitability of sensory neurons in the conditioned stimulus pathway, a simple form of learning [27].
References 1. ^ Grottesi A, Sette M, Palamara T, Rotilio G, Garaci E, Paci M (1998). "The conformation of peptide thymosin alpha 1 in solution and in a membrane-like environment by circular dichroism and NMR spectroscopy. A possible model for its interaction with the lymphocyte membrane". Peptides 19 (10): 1731–8. PMID 9880079. 2. ^ a b PDB 1HJ0; Stoll R, Voelter W, Holak TA (May 1997). "Conformation of thymosin beta 9 in water/fluoroalcohol solution determined by NMR spectroscopy". Biopolymers 41 (6): 623–34. doi:10.1002/(SICI)1097-0282(199705)41:6<623::AID-BIP3>3.0.CO;2-S. PMID 9108730. "The thymosin is β9, bovine orthologue of human β10. Stabilised by organic solvent, the structure was determined by NMR. (Free β-thymosins lack a stable fold in solution)". 3. ^ Goldstein AL (September 2007). "History of the discovery of the thymosins". Ann. N. Y. Acad. Sci. 1112: 1–13. doi:10.1196/annals.1415.045. PMID 17600284. 4. ^ a b Hannappel E (September 2007). "beta-Thymosins". Ann. N. Y. Acad. Sci. 1112: 21–37. doi:10.1196/annals.1415.018. PMID 17468232. 5. ^ Garaci E (September 2007). "Thymosin alpha1: a historical overview". Ann. N. Y. Acad. Sci. 1112: 14–20. doi:10.1196/annals.1415.039. PMID 17567941. 6. ^ Garaci E (September 2007). "Thymosin alpha1: a historical overview". Ann. N. Y. Acad. Sci. 1112: 14–20. doi:10.1196/annals.1415.039. PMID 17567941. 7. ^ Wara DW, Goldstein AL, Doyle NE, Ammann AJ (January 1975). "Thymosin activity in patients with cellular immunodeficiency". N. Engl. J. Med. 292 (2): 70–4. PMID 1078552. 8. ^ Garaci E, Favalli C, Pica F, et al. (September 2007). "Thymosin alpha 1: from bench to bedside". Ann. N. Y. Acad. Sci. 1112: 225–34. doi:10.1196/annals.1415.044. PMID 17600290. 9. ^ Goldstein AL, Goldstein AL (May 2009). "From lab to bedside: emerging clinical applications of thymosin alpha 1". Expert Opin Biol Ther 9 (5): 593–608. doi:10.1517/14712590902911412. PMID 19392576. 10. ^ "Family: Thymosin (PF01290)". Pfam. Wellcome Trust Sanger Institute. http://pfam.sanger.ac.uk/family?acc=PF01290#tabview=tab1. 11. ^ Edwards J (March 2010). "Vertebrate beta-thymosins: conserved synteny reveals the relationship between those of bony fish and of land vertebrates". FEBS Lett. 584 (5): 1047–53. doi:10.1016/j.febslet.2010.02.004. PMID 20138884. 12. ^ Paunola E, Mattila PK, Lappalainen P (February 2002). "WH2 domain: a small, versatile adapter for actin monomers". FEBS Lett. 513 (1): 92–7. PMID 11911886. 13. ^ "Family: WH2 (PF02205)". Pfam. Wellcome Trust Sanger Institute. http://pfam.sanger.ac.uk/family?acc=PF02205#tabview=tab6. 14. ^ Dominguez R (September 2007). "The beta-thymosin/WH2 fold: multifunctionality and structure". Ann. N. Y. Acad. Sci. 1112: 86–94. doi:10.1196/annals.1415.011. PMID 17468236. 15. ^ "Family: WH2 (PF02205)". Pfam. Wellcome Trust Sanger Institute. http://pfam.sanger.ac.uk/family?acc=PF02205#tabview=tab2. 16. ^ Edwards J (August 2004). "Are beta-thymosins WH2 domains?". FEBS Lett. 573 (1-3): 231–2; author reply 233. doi:10.1016/j.febslet.2004.07.038. PMID 15328003. 17. ^ Low TL, Hu SK, Goldstein AL (February 1981). "Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations". Proc. Natl. Acad. Sci. U.S.A. 78 (2): 1162–6. PMID 6940133. 18. ^ Jeffery CJ (January 1999). "Moonlighting proteins". Trends Biochem. Sci. 24 (1): 8–11. PMID 10087914. 19. ^ Tompa P, Szász C, Buday L (September 2005). "Structural disorder throws new light on moonlighting". Trends Biochem. Sci. 30 (9): 484–9. doi:10.1016/j.tibs.2005.07.008. PMID 16054818. 20. ^ Safer D, Elzinga M, Nachmias VT (March 1991). "Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable". J. Biol. Chem. 266 (7): 4029–32. PMID 1999398. 21. ^ Lodish, Harvey F. (2000). "Chapter 18. Cell Motility and Shape I: Microfilaments. 18.2. The Dynamics of Actin Assembly". Molecular cell biology. San Francisco: W.H. Freeman. ISBN 0-7167-3706-X. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mcb.section.5145. 22. ^ Low TL, Hu SK, Goldstein AL (February 1981). "Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations". Proc. Natl. Acad. Sci. U.S.A. 78 (2): 1162–6. PMID 6940133. 23. ^ ="Pekka Lappalainen (2007). Actin-Monomer-Binding Proteins. Boston, MA: Landes Bioscience and Springer Science+Business Media, LLC. ISBN 0-387-46407-7. " 24. ^ ="Dhaese S, Vandepoele K, Waterschoot D, et al. (April 2009). "The mouse thymosin beta15 gene family displays unique complexity and encodes a functional thymosin repeat". J. Mol. Biol. 387 (4): 809–25. doi:10.1016/j.jmb.2009.02.026. PMID 19233202. " 25. ^ "Herrmann D, Hatta M, Hoffmeister-Ullerich SA (November 2005). "Thypedin, the multi copy precursor for the hydra peptide pedin, is a beta-thymosin repeat-like domain containing protein". Mech. Dev. 122 (11): 1183–93. doi:10.1016/j.mod.2005.07.003. PMID 16169708. " 26. ^ Carlier MF, Hertzog M, Didry D, et al. (September 2007). "Structure, function, and evolution of the beta-thymosin/WH2 (WASP-Homology2) actin-binding module". Ann. N. Y. Acad. Sci. 1112: 67–75. doi:10.1196/annals.1415.037. PMID 17947587. ^ "Redell JB, Xue-Bian JJ, Bubb MR, Crow T (August 2007). "One-trial in vitro conditioning regulates an association between the beta-thymosin repeat protein Csp24 and actin". Neuroscience 148 (2): 413–20. doi:10.1016/j.neuroscience.2007.06.023. PMID 17681698. "> | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
