The mitogen-activated protein kinase p38 pathway is conserved in metazoans: Cloning and activation of p38 of the SAPK2 subfamily from the sponge Suberites domuncula

Our recent data suggest that during auto- and allograft recognition in spon ges (Porifera), cytokines are differentially expressed. Since the mitogen-a ctivated protein kinase (MAPK) signal transduction modulates the synthesis and release of cytokines, we intended to identify one key molecule of this pathway. Therefore, a cDNA from the marine sponge Suberites domuncula encod ing the MAPK( was Isolated and analyzed. Its encoded protein is 366 amino a cids long (calculated M-r 42 209), has a TGY dual phosphorylation motif in protein kinase subdomain VIII and displays highest overall similarity to th e mammalian p38 stress activated protein kinase (SAPK2), one subfamily of M APKs. The sponge protein was therefore termed p38_SD. The overall homology (identity and similarity) between p38_SD and human p38 alpha (CSBP2) kinase is 82%. One feature of the sponge kinase is the absence of threonine at po sition 106. In human p38 alpha MAPK this residue is involved in the interac tion with the specific pyridinyl-imidazole inhibitor; T-106 is replaced in p38 SD by methionine. Inhibition studies with the respective inhibitor SE 2 03580 showed that it had no effect on the phosphorylation of the p38 substr ate myelin basic protein. A stress responsive kinase Krs_SD similar to mamm alian Ste20 kinases, upstream regulators of p38, had already previously bee n found in S. domunculla. The S. domuncula p38 MAPK is phosphorylated after treatment of the animal in hypertonic medium. In contrast, exposure of cel ls to hydrogen peroxide, heat shock and ultraviolet light does not cause an y phosphorylation of p38. It is concluded that sponges, the oldest and most simple multicellular animals, utilize the conserved p38 MAPK sig naling pa thway, known to be involved in stress and immune (inflammatory) responses i n higher animals. (C) 2000 Editions scientifiques et medicales Elsevier SAS .