Drosophila SOCS Proteins

Abstract

The importance of signal transduction cascades such as the EGFR and JAK/STAT pathways for development and homeostasis is highlighted by the high levels of molecular conservation maintained between organisms as evolutionary diverged as fruit flies and humans. This conservation is also mirrored in many of the regulatory mechanisms that control the extent and duration of signalling in vivo. One group of proteins that represent important physiological regulators of both EGFR and JAK/STAT signalling is the members of the SOCS family. Only 3 SOCS-like proteins are encoded by the Drosophila genome, and despite this low complexity, Drosophila SOCS proteins share many similarities to their human homologues. SOCS36E is both a target gene and negative regulator of JAK/STAT signalling while SOCS44A and SOCS36E represent positive and negative regulators of EGFR signalling. Here we review our current understanding of Drosophila SOCS proteins, their roles in vivo, and future approaches to elucidating their functions.

Figure 1

Structural conservation of SOCS family proteins. (a) Schematic representation of SOCS proteins. Percentage of conserved amino acids within the regions specified is shown as is protein sizes. Red indicates the SH2 domain and SOCS-box (SB) domain is shown in green. (b) Conservation of the carboxy-terminal regions (including the SH2 and SOCS-box domains) of human and Drosophila SOCS-family proteins is shown as percentage shared identity. Numbers in brackets indicate length of the full-length protein. (c) Phylogram representing common ancestry of full-length SOCS proteins from multiple species as indicated, Drosophila SOCS proteins are in bold. Identities and phylogram shown are generated by the ClustalW2 sequence alignment analysis tool [2].

Figure 2

Expression of SOCS36E is a proxy for JAK/STAT pathway activity and can be used as a pathway reporter. (a) Double fluorescent in situ hybridization demonstrates the association between the expression domains of upd (top and red) and socs36E (middle and green) within a stage 13 embryo. (b) Late third instar wing imaginal disc expressing the 10xSTAT-GFP reporter construct (green) in regions of high JAK/STAT activity that correspond to upd mRNA expression domains [37]. DNA (blue) outlines wing disc morphology.

Figure 3

Schematic representation of the interaction of SOCS proteins with the JAK/STAT and EGFR pathways. Positive regulation indicated by arrows and negative regulation represented by blunt-ended arrows. Dashed line arrow indicates context-specific positive regulation.