Twenty proteins containing a C-terminal SOCS box form five structural classes - PubMed (original) (raw)

Twenty proteins containing a C-terminal SOCS box form five structural classes

D J Hilton et al. Proc Natl Acad Sci U S A. 1998.

Abstract

The four members of the recently identified suppressor of cytokines signaling family (SOCS-1, SOCS-2, SOCS-3, and CIS, where CIS is cytokine-inducible SH2-containing protein) appear, by various means, to negatively regulate cytokine signal transduction. Structurally, the SOCS proteins are composed of an N-terminal region of variable length and amino acid composition, a central SH2 domain, and a previously unrecognized C-terminal motif that we have called the SOCS box. By using the SOCS box amino acid sequence consensus, we have searched DNA databases and have identified a further 16 proteins that contain this motif. These proteins fall into five classes based on the protein motifs found N-terminal of the SOCS box. In addition to four new SOCS proteins (SOCS-4 to SOCS-7) containing an SH2 domain and a SOCS box, we describe three new families of proteins that contain either WD-40 repeats (WSB-1 and -2), SPRY domains (SSB-1 to -3) or ankyrin repeats (ASB-1 to -3) N-terminal of the SOCS box. In addition, we show that a class of small GTPases also contains a SOCS box. The expression of representative members of each class of proteins differs markedly, as does the regulation of expression by cytokines. The function of the WSB, SSB, and ASB protein families remains to be determined.

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Figures

Figure 1

Figure 1

Comparison of the amino acid sequence of the SOCS proteins. (A) Schematic representation of the structures of SOCS, WSB, SSB, ASB, and GTPase proteins. Green bars indicate SH2 domains, blue bars indicate WD-40 repeats, pink bars indicate ankyrin repeats, apricot bars indicate SPRY domains, magenta bars indicate GTPase domains, and yellow bars represent the SOCS box. The shaded bars represent additional less well conserved parts of the proteins. (B) Alignment of N-terminal regions of SOCS, WSB, SSB, and ASB proteins. (C) Alignment of the SH2 domains of CIS and SOCS-1 to SOCS-7. (D) Alignment of the WD-40 repeats of WSB-1, 2. (E) Alignment of the SPRY domains of SSB-1 to SSB-3. (F) Alignment of the ankyrin repeats of ASB-1 to ASB-3. (G) Alignment of the regions between SH2, WD-40, or ankyrin repeats and the SOCS box. (H) Alignment of the SOCS box of the SOCS, WSB, SSB, ASB, and GTPases. X, residues of uncertain identity; •, beginning and end of contigs. Amino acid sequence obtained by conceptual translation of ESTs is approximate only. Residues conserved among 75% or more of the proteins in a given alignment, defined as LIVMA, FYW, DE, QN, CST, KRH, and PG are shaded green in the SH2 domain, blue in the WD-40 repeats, pink in the ankyrin repeats, apricot in the SPRY domain, yellow in the SOCS box, and grey elsewhere in the protein. Alignment of SH2 domains, WD-40 repeats, SPRY domains, and ankyrin repeats has been carried out with reference to previous descriptions of these protein motifs (–17, 19). The sequences for human SOCS-6 and SOCS-7 were obtained from the following GenBank entries describing CIS4 and and Nck/Ash binding protein (GenBank accession nos. AB006968 and AB005216).

Figure 1

Figure 1

Comparison of the amino acid sequence of the SOCS proteins. (A) Schematic representation of the structures of SOCS, WSB, SSB, ASB, and GTPase proteins. Green bars indicate SH2 domains, blue bars indicate WD-40 repeats, pink bars indicate ankyrin repeats, apricot bars indicate SPRY domains, magenta bars indicate GTPase domains, and yellow bars represent the SOCS box. The shaded bars represent additional less well conserved parts of the proteins. (B) Alignment of N-terminal regions of SOCS, WSB, SSB, and ASB proteins. (C) Alignment of the SH2 domains of CIS and SOCS-1 to SOCS-7. (D) Alignment of the WD-40 repeats of WSB-1, 2. (E) Alignment of the SPRY domains of SSB-1 to SSB-3. (F) Alignment of the ankyrin repeats of ASB-1 to ASB-3. (G) Alignment of the regions between SH2, WD-40, or ankyrin repeats and the SOCS box. (H) Alignment of the SOCS box of the SOCS, WSB, SSB, ASB, and GTPases. X, residues of uncertain identity; •, beginning and end of contigs. Amino acid sequence obtained by conceptual translation of ESTs is approximate only. Residues conserved among 75% or more of the proteins in a given alignment, defined as LIVMA, FYW, DE, QN, CST, KRH, and PG are shaded green in the SH2 domain, blue in the WD-40 repeats, pink in the ankyrin repeats, apricot in the SPRY domain, yellow in the SOCS box, and grey elsewhere in the protein. Alignment of SH2 domains, WD-40 repeats, SPRY domains, and ankyrin repeats has been carried out with reference to previous descriptions of these protein motifs (–17, 19). The sequences for human SOCS-6 and SOCS-7 were obtained from the following GenBank entries describing CIS4 and and Nck/Ash binding protein (GenBank accession nos. AB006968 and AB005216).

Figure 2

Figure 2

Northern blot analysis of mRNA expression of mouse SOCS-1, SOCS-5, WSB-2, and ASB-1 in normal adult mouse tissues and in mouse embryos. Northern blot analysis of poly(A)+ mRNA extracted from a range of adult mouse tissues (Left) and mouse embryos and yolk sac (Right) as described (4). Sal. Gland, salivary gland; MLN, mesenteric lymph node; E9–E18, embryos from the 9th through to the 18th day of gestation; P1, 1 day after birth. Size markers in kilobases (kb) are shown to the left of the figure, and the identity of probes is shown to the right.

Figure 3

Figure 3

Northern blot analysis of mRNA expression of mouse SOCS-1, SOCS-5, WSB-2, and ASB-1 in the mouse liver before and various times after injection of IL-6. Northern blot analysis of poly(A)+ mRNA expression in the liver of mice injected with saline (sal) or IL-6. Mice were injected intravenously with 200 μl of IL-6 (25 μg/ml) or saline. At the times indicated, mice were killed, their livers were removed, and mRNA was extracted as described (4). Size markers in kilobases (kb) are shown to the left of the figure and the identity of probes is shown to the right.

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References

    1. Nicola N A, editor. Guidebook to Cytokines and Their Receptors. Oxford: Oxford Univ. Press; 1994.
    1. Darnell J E, Jr, Kerr I M, Stark G R. Science. 1994;264:1415–1421. - PubMed
    1. Ihle J N, Kerr I M. Trends Genet. 1995;11:69–74. - PubMed
    1. Starr R, Willson T A, Viney E M, Murray L J, Rayner J R, Jenkins B J, Gonda T J, Alexander W S, Metcalf D, Nicola N A, Hilton D J. Nature (London) 1997;387:917–921. - PubMed
    1. Endo T A, Masuhara M, Yokouchi M, Suzuki R, Mitsui K, Sakamoto H, Ohtsubo M, Misawa H, Kanekura Y, Yoshimura A. Nature (London) 1997;387:921–924. - PubMed

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