Receptor protein-tyrosine phosphatases: origin of domains (catalytic domain, Ig-related domain, fibronectin type III module) based on the sequence ofthe sponge Geodia cydonium

Reversible tyrosine phosphorylation of proteins is one of the major regulat ory physiological events in response to cell-cell- and cell-matrix contact in Metazoa. Previously it was documented that the tyrosine phosphorylating enzymes, the tyrosine kinases (TKs), are autapomorphic characters of Metazo a, including sponges. In this paper the tyrosine dephosphorylating enzymes, the protein-tyrosine phosphatases (PTPs), are studied which can be grouped into two subfamilies, the soluble PTPs and the receptor PTPs (RPTPs). PTPs are characterized by one PTPase domain which interestingly comprises seque nce similarity to yeast PTPs. In contrast to the PTPs, the RPTPs - which ha ve been found only in Metazoa - are provided with two PTPase domains. To st udy the evolution of the RPTPs the full-length size RPTP was cloned from th e marine demosponge Geodia cydonium, the phylogenetic oldest metazoan taxon . The 3253 bp long sequence has a putative open reading frame coding for a 999 aa long RPTP which is characterized by two fibronectin (type III: FN-II I) domains in the extracellular portion, one intracellular immunoglobulin ( Ig)-related domain, and two PTPase domains. Phylogenetic analysis revealed that the sponge FN-III domains form the basis of the metazoan FN-III domain with the common metazoan ancestor. The Ig-related, typical metazoan, modul e is classified to the disulphide lacking Ig members and represents the phy logenetic earliest member of this group. The beta -sheet propensity was cal culated and the characteristic amino acids an present in the seven P-sheets . The analysis of the two PTPase domains of the sponge RPTP demonstrates th at the first domain is closely related to the PTPase domains present in the soluble PTPs, while the second PTPase domain is only distantly related to them. By constructing a rooted phylogenetic cladogram it became overt that the duplication of the PTPase domains must have occurred already in yeast. This interesting finding indicates that two conserved PTPase domains origin ated from a common ancestor in yeast while the evolutionary novelties, the FN-III domains and the Ig-related module, were added during;he transition t o the Metazoa. Hence, the tyrosine dephosphorylating enzyme, RPTP, is an ex ample for a modular protein which is composed of ancient modules (PTPase do main[s]) and two metazoan novelties, while the tyrosine phosphorylating enz ymes, the TKs, evolved only in Metazoa. (C) 2001 Elsevier Science B.V. All rights reserved.