Dataset Information

Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides.

ABSTRACT: Two isoforms of human interleukin 15 (IL-15) exist. One isoform has a shorter putative signal peptide (21 amino acids) and its transcript shows a tissue distribution pattern that is distinct from that of the alternative IL-15 isoform with a 48-aa signal peptide. The 21-aa signal isoform is preferentially expressed in tissues such as testis and thymus. Experiments using different combinations of signal peptides and mature proteins (IL-2, IL-15, and green fluorescent protein) showed that the short signal peptide regulates the fate of the mature protein by controlling the intracellular trafficking to nonendoplasmic reticulum sites, whereas the long signal peptide both regulates the rate of protein translation and functions as a secretory signal peptide. As a consequence, the IL-15 associated with the short signal peptide is not secreted, but rather is stored intracellularly, appearing in the nucleus and cytoplasmic components. Such production of an intracellular lymphokine is not typical of other soluble interleukin systems, suggesting a biological function for IL-15 as an intracellular molecule.

SUBMITTER: Tagaya Y

PROVIDER: S-EPMC25016 | biostudies-literature | 1997 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides.

Tagaya Y Y Kurys G G Thies T A TA Losi J M JM Azimi N N Hanover J A JA Bamford R N RN Waldmann T A TA

Proceedings of the National Academy of Sciences of the United States of America 19971201 26

Two isoforms of human interleukin 15 (IL-15) exist. One isoform has a shorter putative signal peptide (21 amino acids) and its transcript shows a tissue distribution pattern that is distinct from that of the alternative IL-15 isoform with a 48-aa signal peptide. The 21-aa signal isoform is preferentially expressed in tissues such as testis and thymus. Experiments using different combinations of signal peptides and mature proteins (IL-2, IL-15, and green fluorescent protein) showed that the short ...[more]

PMID: 9405632

Similar Datasets

Project description:Eukaryotic translation initiation factor 4GI (eIF4GI) is an essential protein that is the target for translational regulation in many cellular processes and viral systems. It has been shown to function in both cap-dependent and cap-independent translation initiation by recruiting the 40S ribosomal subunit to the mRNA cap structure or internal ribosome entry site (IRES) element, respectively. Interestingly eIF4GI mRNA itself has been reported to contain an IRES element in its 5' end that facilitates eIF4GI protein synthesis via a cap-independent mechanism. In HeLa cells, eIF4GI exists as several isoforms that differ in their migration in sodium dodecyl sulfate (SDS) gels; however, the nature of these isoforms was unclear. Here, we report a new cDNA clone for eIF4GI that extends the 5' sequence 340 nucleotides beyond the previously published sequence. The new extended sequence of eIF4GI is located on chromosome 3, within two additional exons immediately upstream of the previously published eIF4GI sequence. When mRNA transcribed from this cDNA clone was translated in vitro, five eIF4GI polypeptides were generated that comigrated in SDS-polyacrylamide gels with the five isoforms of native eIF4GI. Furthermore, translation of eIF4GI-enhanced green fluorescent protein fusion constructs in vitro or in vivo generated five isoforms of fusion polypeptides, suggesting that multiple isoforms of eIF4GI are generated by alternative translation initiation in vitro and in vivo. Mutation of two of the five in-frame AUG residues in the eIF4GI cDNA sequence resulted in loss of corresponding polypeptides after translation in vitro, confirming alternate use of AUGs as the source of the multiple polypeptides. The 5' untranslated region of eIF4GI mRNA also contains an out-of-frame open reading frame (ORF) that may down-regulate expression of eIF4GI. Further, data are presented to suggest that a proposed IRES embedded in the eIF4GI ORF is able to catalyze synthesis of multiple eIF4GI isoforms as well. Our data suggest that expression of the eIF4GI isoforms is partly controlled by a complex translation strategy involving both cap-dependent and cap-independent mechanisms.

Project description:Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are epithelial cells, not immune cells. We examined IL-22 signal transduction in oral squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that IL-22R was expressed more highly in OSCC compared to normal regions. An IL-22R signal was also observed in metastatic OSCC cells in the lymph node. RT-PCR showed that the human OSCC cell lines MISK81-5, HSC-3, HSC-4, SAS and SQUU-B expressed IL-22 receptor chains. Immunoblotting showed that IL-22 induced a transient tyrosine phosphorylation of STAT3 (pY705-STAT3) in MISK81-5 cells. The change in the serine phosphorylation of STAT3 was subtle during the examination periods. Simultaneously, pY705-STAT3 activation in HSC-3 cells was undetectable after IL-22 stimulation. Immunocytochemistry demonstrated that IL-22 induced the translocation of phosphorylated STAT3 into the nucleus of MISK81-5 cells. IL-22 temporarily upregulated the expression of anti-apoptotic and mitogenic genes such as Bcl-x, survivin and c-Myc, as well as SOCS3. IL-22 transiently activated ERK1/2 and induced a delayed phosphorylation of p38 MAP kinase, but negligibly involved the activation of NF-?B in MISK81-5 cells. MISK81-5 and SQUU-B cells treated with IL-22 showed mild cellular proliferation. MISK81-5, HSC-4 and SAS cells treated with IL-22 downregulated the keratinocyte differentiation-related genes compared with unstimulated cells. Conversely, STAT3 suppression by STAT3 siRNA strongly disrupted the downregulation of these genes by IL-22, but it did not significantly affect the activation of ERK1/2 by IL-22. The OSCC cells used in this study upregulated the expression of SERPINB3/4 (SCCA1/2), well-known SCC markers, following treatment with IL-22. These results indicate that IL-22 differentially activates the STAT3 signaling system depending on the type of OSCC. IL-22 may therefore play a role in tumor growth, cell differentiation and progression through STAT3-dependent and -independent pathways.

Dataset Information

Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides.

Publications

Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets