CHARACTERIZATION AND PHYLOGENETIC ANALYSIS OF A CDNA-ENCODING THE FESFER RELATED, NONRECEPTOR PROTEIN-TYROSINE KINASE IN THE MARINE SPONGESYCON RAPHANUS/

In search of ancient versions of phylogenetically conserved genes/prot eins, which are typical for multicellular animals, we have decided to analyse marine sponges (Porifera), the most ancient and most primitive metazoan organisms. We report here the complete nucleotide sequence o f Sycon raphanus cDNA coding for a 879 aa long protein (100 kDa), whic h displays high overall similarity in primary structure and organizati on of domains with non-receptor tyrosine kinases (TKs) from the Fes/FE R family. The encoded protein, which we named Fes/FER_SR, has a highly conserved, 260 aa long tyrosine kinase domain at the C-terminus. Amin o-terminal to the catalytic domain is an 85 aa long SH2 domain. The N- terminus is over 500 aa long and displays homology only with N-termina l domains of protein-tyrosine kinases (PTKs) from the Fes/FER family. Mammalian Fes/FER proteins show around 58% overall homology with Fes/F ER_SR (identity and similarity) and lower homology was found with Dros ophila melanogaster Fps (FER) protein (49%). Homologies in TK, SH2 and N-terminal domains are on average 78%, 65% and 49%, respectively. Fes /FER_SR shows next to best homology with the Abl family of non-recepto r PTKs, while Src-related PTKs from the fresh-water sponge Spongilla l acustris are related only distantly to Fes/FER_SR. Phylogenetic analys is shows that the S. raphanus TK is indeed the most ancient known memb er of the Fes/FER family of non-receptor PTKs. The role of these PTKs in signal transduction in higher animals is still enigmatic; they are present in the nucleus as well as in the cytoplasm and FER is found in all cell types examined. The function of Fes/FER_SR in sponge, the mo st primitive multicellular animal which lacks specialized organ system s, remains to be elucidated. (C) 1998 Elsevier Science B.V. All rights reserved.