Figure 1

Sequence alignment and domain analysis of S. mansoni p38 MAPK. The S. mansoni putative p38 MAPK sequence (XP_002571000) was aligned with those for S. japonicum MAPK14a, Homo sapiens (p38 MAPKα, also known as MAPK14 isoform 1), Drosophila melanogaster (p38a MAPK and p38b MAPK), Caenorhabditis elegans (p38 MAPK family member, PMK1) and Danio rerio (MAPK 14a); accession numbers are shown. Multiple alignments were achieved using Geneious Pro 4.85 with Blosum62 cost matrix and default settings; shading of residues: black = 100% similar, dark grey = 80-100% similar, light grey = 60-80% similar and white < 60% similar. The ATP binding site, kinase interacting motif (KIM) docking site, and activation loop are indicated by coloured arrows. Within the activation loop, the conserved Thr-Gly-Tyr (TGY) phosphorylation motif is highlighted by the yellow box, with the phosphorylated residues (Thr and Tyr) central to kinase activation indicated with green asterisks; the substrate binding site is shown by the orange box. Sequence highlighted by the blue box is that used to generate the monoclonal anti-phospho p38 MAPK antibodies. The residues within the ATP binding site that are known to confer specificity and sensitivity of SB 230580 towards p38 MAPK are highlighted by the red box with the residue (Thr) most responsible for p38 MAPK inhibition indicated by the red asterisk; red crosses denote other known interaction sites between SB 203580 and p38 MAPK (see text for further details).