Biological activities of thymosin ß₄defined by active sites in short peptide sequences

Abstract

Thymosin beta(4), a small ubiquitous protein containing 43 aa, has structure/function activity via its actin-binding domain and numerous biological affects on cells. Since it is the major actin-sequestering molecule in eukaryotic cells and is found essentially in all cells and body fluids, thymosin beta(4) has the potential for significant roles in tissue development, maintenance, repair, and pathology. Several active sites with unique functions have been identified, including the amino-terminal site containing 4 aa (Ac-SDKP) that generally blocks inflammation and reduces fibrosis. Another active site at the amino terminus contains 15 aa, including Ac-SDKP, and promotes cell survival and blocks apoptosis, while a short sequence containing LKKTETQ, the central actin-binding domain (aa 17-23) plus 1 additional amino acid (Q), promotes angiogenesis, wound healing, and cell migration. Several additional biological activities have been identified but not yet localized in the molecule, including its antimicrobial activity, the induction of various genes (including laminin-5, MMPs, TGF beta, zyxin, terminal deoxynucleotidyl transferase, and angiogenesis-related proteins), and the ability to activate ILK/PINCH/Akt, and other signaling molecules important in both apoptosis and inflammatory pathways. This review details these important physiologically and pathologically active sites and their potential therapeutic uses.

Perfusable branching microvessel bed for vascularization of engineered tissues

“…1 C and D). Although Tβ4 alone can stimulate EC migration and differentiation (14,23), Tβ4 also stimulates the synthesis and autocrine secretion of VEGF, as previously reported (24). Here, we observed enhanced VEGF secretion from explants cultivated on Tβ4 hydrogels compared with Tβ4-free gels ( Fig.…”

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

“…In addition to effects on hematopoiesis, AcSDKP has been implicated in other physiologic processes, including promoting angiogenesis (Sosne et al, 2010;Myöhänen et al, 2011). Several studies have demonstrated that AcSDKP inhibits fibroblast proliferation in the myocardium, aorta, and kidney following injury (Peng et al, 2001;Lin et al, 2008;Liao et al, 2010).…”

The peptide network regulated by angiotensin converting enzyme (ACE) in hematopoiesis

“…49 The precursor peptide thymosin β4 is present in all cells except red blood cells and in all body fluids (saliva, tears, blood, plasma, wound fluid). 50 Thymosin β4 is induced during GM-CSF driven BM differentiation. 51 Murine BM endothelial cells, a component of BM stroma, secrete thymosin β4 and Ac-SDKP into the culture media.…”