Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibronectin contains at least two distinct oligopeptide sequences serving as signals for the interaction with cell surface adhesion receptors termed integrins. One of these sequences, Arg-Gly-Asp-Ser (RGDS) tetrapeptide, was shown to be transferred to a truncated form of Staphylococcal IgG-binding protein (hereafter referred to as tSPA) with retention of its cell-adhesive activity [Maeda, T. et al. (1989) J. Biol. Chem. 264, 15165-15168]. We have extended the observation to another cell-adhesive sequence, Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (referred to as "CS1" sequence), to demonstrate that: i) the tSPA grafted with the sequence mediated adhesion of human lymphoma and rhabdomyosarcoma cells, mouse melanoma cells, but not of hamster fibroblasts; ii) antibodies against integrin alpha 4 and beta 1 subunits specifically inhibited cell adhesion mediated by the CS1-grafted tSPA; iii) a heterodivalent tSPA grafted with both RGDS and CS1 sequences at different sites was more potent in promoting cell adhesion than the monovalent tSPAs grafted with either sequence alone. These results indicate that not only the RGDS but also the CS1 sequence can be transferred to tSPA with retention of its cell-adhesive activity as well as its cell-type specificity, and that the grafted CS1 sequence is recognized by the same integrin isotype as the authentic sequence within intact fibronectin.
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PMID:Engineering of artificial cell-adhesive proteins by grafting EILDVPST sequence derived from fibronectin. 845 70

IGF binding protein (IGFBP)-6 is a member of the IGFBP family that regulates the actions of IGFs. Although IGFBPs exert their functions extracellularly in an autocrine/paracrine manner, several members of the family, such as IGFBP-3 and -5, possess nuclear localization signals (NLS). To date, no NLS has been described for IGFBP-6, an IGFBP that binds preferentially to IGF-II. We report here that both exogenous and endogenous IGFBP-6 could be imported into the nuclei of rhabdomyosarcoma and HEK-293 cells. Nuclear import of IGFBP-6 was mediated by a NLS sequence that bears limited homology to those found in IGFBP-3 and -5. IGFBP-6 nuclear translocation was an active process that required importins. A peptide corresponding to the IGFBP-6 NLS bound preferentially to importin-alpha. A comprehensive peptide array study revealed that, in addition to positively charged residues such as Arg and Lys, amino acids, notably Gly and Pro, within the NLS, played an important part in binding to importins. Overexpression of wild-type IGFBP-6 increased apoptosis, and the addition of IGF-II did not negate this effect. Only the deletion of the NLS segment abolished the apoptosis effect. Taken together, these results suggest that IGFBP-6 is translocated to the nucleus with functional consequences and that different members of the IGFBP family have specific nuclear import mechanisms.
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PMID:A functional nuclear localization signal in insulin-like growth factor binding protein-6 mediates its nuclear import. 1803 85