title: Biological activities of thymosin beta4 defined 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.
authors.affiliation: Department of Opthalmology and Anatomy/Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA. gsosne@med.wayne.edu
authors.forename: Gabriel
authors.initials: G
authors.lastname: Sosne
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.forename: Allan L
authors.initials: AL
authors.lastname: Goldstein
authors.forename: Michelle
authors.initials: M
authors.lastname: Wheater
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D010455:Peptides; D013947:Thymosin / Q000737:chemistry / Q000502:physiology*; D000099201:Thymosin beta(4)
chemical_list: D010455:Peptides; D013947:Thymosin; D000099201:Thymosin beta(4)