Conservation of Epidermal Growth Factor Receptor Function in the Human Parasitic Helminth Schistosoma mansoni

Abstract

The epidermal growth factor receptor (EGF-R) plays an important role in development and cell differentiation, and homologues of EGF-R have been identified in a broad range of vertebrate and invertebrate organisms. This work concerns the functional characterization of SER, the EGF-R-like molecule previously identified in the helminth parasite Schistosoma mansoni (Shoemaker, C. B., Ramachandran, H., Landa, A., dos Reis, M. G., and Stein, L. D. (1992) Mol. Biochem. Parasitol. 53, 17–32). Transactivation assays performed in epithelial Madin-Darby canine kidney cells co-transfected with SER and a Ras-responsive reporter vector indicated that SER was able a in epidermal growth factor in that in was receptor and with of SER and of performed of the receptor of the SER in mansoni was of the of the SER receptor vertebrate the the of EGF-R in was and in the that The role of SER a receptor and in and parasite development The epidermal growth factor receptor (EGF-R) plays an important role in development and cell differentiation, and homologues of EGF-R have been identified in a broad range of vertebrate and invertebrate organisms. This work concerns the functional characterization of SER, the EGF-R-like molecule previously identified in the helminth parasite Schistosoma mansoni (Shoemaker, C. B., Ramachandran, H., Landa, A., dos Reis, M. G., and Stein, L. D. (1992) Mol. Biochem. Parasitol. 53, 17–32). Transactivation assays performed in epithelial Madin-Darby canine kidney cells co-transfected with SER and a Ras-responsive reporter vector indicated that SER was able a in epidermal growth factor in that in was receptor and with of SER and of performed of the receptor of the SER in mansoni was of the of the SER receptor vertebrate the the of EGF-R in was and in the that The role of SER a receptor and in and parasite development The epidermal growth factor receptor (EGF-R) epidermal growth factor epidermal growth Madin-Darby canine epidermal growth factor epidermal growth Madin-Darby canine a of cell development and EGF-R was the receptor L. and and have been EGF-R the of receptor with an with and an of EGF-R have been and and a of epidermal growth factor D. Mol. the receptor the of and of receptor that and and in the and in Mol. EGF-R a the The the and the of of EGF-R and the of EGF-R in been EGF-R of the in EGF-R in been in M. in L. D. in the and and in the indicated that the EGF-R in C. and D. the role of the EGF-R in invertebrate the Schistosoma mansoni EGF-R of the receptor that have been in parasite dos Mol. Biochem. Parasitol. M. C. C. Mol. Biochem. Parasitol. SER in that in development and Mol. Biochem. Parasitol. EGF-R the the the work that SER in cells and was of was in the parasite Mol. Biochem. Parasitol. have a functional of SER the and role a receptor The of the SER been in vertebrate cells and the of the parasite receptor and and an SER was the and the of parasite was in the that in the The role of SER a receptor and in and parasite development of mansoni was and and previously C. in in M. Parasitol. of was mansoni the of and a The was the and the and the and of the SER in the was with vector and the vector the and an SER of the a the The and in assays performed with D. C. C. D. cells in and a and in of with of a of reporter vector C. D. D. and of cells with of of cells in and in in the in cells a performed with in was the SER and the and the EGF-R was of in in of and of was a with of the of and of the of of SER in with and in and with with and a with of was in in the of SER, and in was the of a the of the of was the of the and of SER in of SER in was of the previously D. with SER in in and and and in and the with in and a and The of SER was performed in SER and in of and the and and the of in was performed previously Biochem. with of SER with of of in and in and was and of the in in a of in the of and the of the of and the of in in and the was of and was the of was performed The was the of and SER was of SER in mansoni in and and in of with and in with and with of and and the of the receptor Mol. Biochem. Parasitol. and in and was and and the of and the the and the mansoni and and SER and the and in of and the the with the in in a of in the of of of and of and was in the a and a was a cell and a was performed with the of of was of the of of and with and was SER in SER was the vector and in epithelial assays of cell with that the was an able and Mol. Biochem. Parasitol. Transactivation assays performed in cells co-transfected with the reporter This vector Ras-responsive with of a with the and the reporter C. D. D. This been a functional of receptor D. C. C. D. in indicated that in able the in a with with of cells with the a of was and in the of was of the canine that SER in cells was able a in the of in cells was the of receptor and in in and have been with mansoni C. M. D. C. Mol. Biochem. Parasitol. cells an the of the SER in that of SER in was in of the of the SER was in The of an that the a of the receptor the cell and of SER in with SER, and and The of in have been a receptor and the of the and of receptor the and of the and The in that in a of the EGF-R was in in in the of performed with that was able in with that The of in was that in SER the that SER was in with a SER in in that a in the of the receptor in of that the SER was a the receptor of in of of that been SER, with of was performed a of the of SER, receptor and of SER SER and and was of SER and was the of of in of SER, with The of and indicated in the of the SER, that the of in receptor in the of SER the receptor and have the of the of in a of in and the of SER the in was the of in of the of SER of in cells and of that SER with performed the of the receptor in and a of of SER This was that the receptor of with of SER with was and was performed and a of of SER and receptor was of the SER in work the of the SER in and in parasite Mol. Biochem. Parasitol. the of the parasite receptor and with and in that a of in with the in of a with an of the of the of identified the SER and of the SER The of SER in assays that the of Mol. Biochem. Parasitol. and of The in of and SER in and of SER in of with and assays of was in in of with identified the of in a a functional of SER in have the of SER in the mansoni parasite in the and the of in the of SER in in in the that SER the parasite that of in with EGF-R been in The that SER was in the and of in the a of in that in of with and in a with a a a of with the a in the of with that a in the that a of was able in in of SER in the of of SER was performed of and of and the the with the of the of mansoni and in the of of of with of in been in the of in development and the role of growth factor in the invertebrate L. D. and C. M. The of an receptor molecule in mansoni dos Mol. Biochem. Parasitol. Mol. Biochem. Parasitol. role in and in the parasite and in the functional and of receptor and the of in mansoni development in SER and with of the EGF-R The of SER and previously been Mol. Biochem. Parasitol. The in was of was and Mol. Biochem. Parasitol. have functional characterization of the SER receptor and with have the SER in vertebrate epithelial cells and the of Transactivation in epithelial cells a the functional of receptor a D. C. C. D. was and of the receptor D. Mol. This a of and the with a vector a of the of the in the The have the of and the the of in and have that the receptor in the of and was able The that EGF-R was in was an SER in cells indicated that in cells with cells The was and a was of in and This the of the of receptor and of SER that SER was able a in the that of SER a of and the of a receptor the of SER in the the of receptor in a in the of the SER the of that receptor was indicated that the parasite receptor was in the of epithelial cells and and that with the of the vertebrate of that SER and a and a the of a functional in the SER of the of SER the the of of the SER EGF-R with the of the dos Mol. Biochem. Parasitol. an SER a of in that a of the of the EGF-R work with and functional SER and the characterization of able in of SER a of the parasite receptor the vertebrate of the in cells SER of the canine receptor in epithelial cells the receptor in in that the of SER in was of the of that of the receptor the that a growth factor receptor able the vertebrate The that the SER was the of the and have the of a mansoni of the growth factor receptor a in growth factor in was a of growth factor with a functional of the receptor the receptor Mol. Biochem. Parasitol. with the receptor the the of in and the that development with parasite performed in the of mansoni in the of of and the of and The have been with that in C. C. C. C. Parasitol. in work that and in with of assays performed indicated that in that in and the The that SER was in Mol. Biochem. Parasitol. a in with the of SER the the that SER in a the and previously Mol. Biochem. Parasitol. in the of that was able in with a of the of indicated the that the SER molecule was parasite and and in the of in the of the receptor vertebrate and a vertebrate the of the role of in in the of a of SER an important role in development and an of the of SER and with EGF-R the of that and the The epidermal growth factor receptor (EGF-R) epidermal growth factor epidermal growth Madin-Darby canine epidermal growth factor epidermal growth Madin-Darby canine a of cell development and EGF-R was the receptor L. and and have been EGF-R the of receptor with an with and an of EGF-R have been and and a of epidermal growth factor D. Mol. the receptor the of and of receptor that and and in the and in Mol. EGF-R a the The the and the of of EGF-R and the of EGF-R in been EGF-R of the in EGF-R in been in M. in L. D. in the and and in the indicated that the EGF-R in C. and D. the role of the EGF-R in invertebrate SER, the Schistosoma mansoni EGF-R of the receptor that have been in parasite dos Mol. Biochem. Parasitol. M. C. C. Mol. Biochem. Parasitol. SER in that in development and Mol. Biochem. Parasitol. EGF-R the the the work that SER in cells and was of was in the parasite Mol. Biochem. Parasitol. have a functional of SER the and role a receptor The of the SER been in vertebrate cells and the of the parasite receptor and and an SER was the and the of parasite was in the that in the The role of SER a receptor and in and parasite development of mansoni was and and previously C. in in M. Parasitol. of was mansoni the of and a The was the and the and the and of the SER in the was with vector and the vector the and an SER of the a the The and in assays performed with D. C. C. D. cells in and a and in of with of a of reporter vector C. D. 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D. and of cells with of of cells in and in in the in cells a performed with in was the SER and the and the EGF-R was of in in of and of was a with of the of and of the of of SER in with and in and with with and a with of was in in the of SER, and in was the of a the of the of was the of the and of SER in of SER in was of the previously D. with SER in in and and and in and the with in and a and The of SER was performed in SER and in of and the and and the The of in was performed previously Biochem. with of SER with of of in and in and was and of the in in a of in the of and the of the of and the of in in and the was of and was the of was performed The was the of and SER was of SER in mansoni in and and in of with and in with and with of and and the of the receptor Mol. Biochem. Parasitol. and in and was and and the of and the the and the mansoni and and SER and the and in of and the the with the in in a of in the of of of and of and was in the a and a was a cell and a was performed with the of of was of the of of and with and was SER in SER was the vector and in epithelial assays of cell with that the was an able and Mol. Biochem. Parasitol. Transactivation assays performed in cells co-transfected with the reporter This vector Ras-responsive with of a with the and the reporter C. D. D. This been a functional of receptor D. C. C. D. in indicated that in able the in a with with of cells with the a of was and in the of was of the canine that SER in cells was able a in the of in cells was the of receptor and in in and have been with mansoni C. M. D. C. Mol. Biochem. Parasitol. cells an the of the SER in that of SER in was in of the of the SER was in The of an that the a of the receptor the cell and of in have been a receptor and the of the and of receptor the and of the and The in that in a of the EGF-R was in in in the of performed with that was able in with that The of in was that in SER the that SER was in with a SER in in that a in the of the receptor in of that the SER was a the receptor of in of of that been SER, with of was performed a of the of SER, receptor and of SER SER and and was of SER and was the of of in of SER, with The of and indicated in the of the SER, that the of in receptor in the of SER the receptor and have the of the of in a of in and the of SER the in was the of in of the of SER of in cells and of that SER with performed the of the receptor in and a of of SER This was that the receptor of with of SER with was and was performed and a of of SER and receptor was of the SER in work the of the SER in and in parasite Mol. Biochem. Parasitol. the of the parasite receptor and with and in that a of in with the in of a with an of the of the of identified the SER and of the SER The of SER in assays that the of Mol. Biochem. Parasitol. and of The in of and SER in and of SER in of with and assays of was in in of with identified the of in a a functional of SER in have the of SER in the mansoni parasite in the and the of in the of SER in in in the that SER the parasite that of in with EGF-R been in The that SER was in the and of in the a of in that in of with and in a with a a a of with the a in the of with that a in the that a of was able in in of SER in the of of SER was performed of and of and the the with the of the of mansoni and in the of of of with of in SER in SER was the vector and in epithelial assays of cell with that the was an able and Mol. Biochem. Parasitol. Transactivation assays performed in cells co-transfected with the reporter This vector Ras-responsive with of a with the and the reporter C. D. D. This been a functional of receptor D. C. C. D. in indicated that in able the in a with with of cells with the a of was and in the of was of the canine that SER in cells was able a in the of in cells was the of receptor and in in and have been with mansoni C. M. D. C. Mol. Biochem. Parasitol. cells an the of the SER in that of SER in was in of the of the SER was in The of an that the a of the receptor the cell and of in have been a receptor and the of the and of receptor the and of the and The in that in a of the EGF-R was in in in the of performed with that was able in with that The of in was that in SER the that SER was in with a SER in in that a in the of the receptor in of that the SER was a the receptor SER in the of the SER, that the of in receptor in the of SER the receptor and have the of the of in a of in and the of SER the in was the of in of the of SER of in cells and of that SER with performed the of the receptor in and a of of SER This was that the receptor of the SER in work the of the SER in and in parasite Mol. Biochem. Parasitol. the of the parasite receptor and with and in that a of in with the in of a with an of the of the of identified the SER and of the SER The of SER in assays that the of Mol. Biochem. Parasitol. and of The in of and SER in and of in a a functional of SER in have the of SER in the mansoni parasite in the and the of in the of SER in in in the that SER the parasite that of in with EGF-R been in The that SER was in the and of in the a of in that in of with and in a with a a a of with the a in the of with that a in the that a of was able in in been in the of in development and the role of growth factor in the invertebrate L. D. and C. M. The of an receptor molecule in mansoni dos Mol. Biochem. Parasitol. Mol. Biochem. Parasitol. role in and in the parasite and in the functional and of receptor and the of in mansoni development in SER and with of the EGF-R The of SER and previously been Mol. Biochem. Parasitol. The in was of was and Mol. Biochem. Parasitol. have functional characterization of the SER receptor and with have the SER in vertebrate epithelial cells and the of Transactivation in epithelial cells a the functional of receptor a D. C. C. D. was and of the receptor D. Mol. This a of and the with a vector a of the of the in the The have the of and the the of in and have that the receptor in the of and was able The that EGF-R was in was an SER in cells indicated that in cells with cells The was and a was of in and This the of the of receptor and of SER that SER was able a in the that of SER a of and the of a receptor the of SER in the the of receptor in a in the of the SER the of that receptor was indicated that the parasite receptor was in the of epithelial cells and and that with the of the vertebrate of that SER and a and a the of a functional in the SER of the of SER the the of of the SER EGF-R with the of the dos Mol. Biochem. Parasitol. an SER a of in that a of the of the EGF-R work with and functional SER and the characterization of able in of SER a of the parasite receptor the vertebrate of the in cells SER of the canine receptor in epithelial cells the receptor in in that the of SER in was of the of that of the receptor the that a growth factor receptor able the vertebrate The that the SER was the of the and have the of a mansoni of the growth factor receptor a in growth factor in was a of growth factor with a functional of the receptor the receptor Mol. Biochem. Parasitol. with the receptor the the of in and the that development with parasite performed in the of mansoni in the of of and the of and The have been with that in C. C. C. C. Parasitol. in work that and in with of assays performed indicated that in that in and the The that SER was in Mol. Biochem. Parasitol. a in with the of SER the the that SER in a the and previously Mol. Biochem. Parasitol. in the of that was able in with a of the of indicated the that the SER molecule was parasite and and in the of in the of the receptor vertebrate and a vertebrate the of the role of in in the of a of SER an important role in development and an of the of SER and with EGF-R the of that and the been in the of in development and the role of growth factor in the invertebrate L. D. and C. M. The of an receptor molecule in mansoni dos Mol. Biochem. Parasitol. Mol. Biochem. Parasitol. role in and in the parasite and in the functional and of receptor and the of in mansoni development in The SER and with of the EGF-R The of SER and previously been Mol. Biochem. Parasitol. The in was of was and Mol. Biochem. Parasitol. have functional characterization of the SER receptor and with have the SER in vertebrate epithelial cells and the of Transactivation in epithelial cells a the functional of receptor a D. C. C. D. was and of the receptor D. Mol. This a of and the with a vector a of the of the in the The have the of and the the of in and have that the receptor in the of and was able The that EGF-R was in was an SER in cells indicated that in cells with cells The was and a was of in and This the of the of receptor and of SER that SER was able a in the that of SER a of and the of a receptor the of SER in the the of receptor in a in the of the SER the of that receptor was indicated that the parasite receptor was in the of epithelial cells and and that with the of the vertebrate of that SER and a and a the of a functional in the SER of the of SER the the of of the SER EGF-R with the of the dos Mol. Biochem. Parasitol. an SER a of in that a of the of the EGF-R work with and functional SER and the characterization of able in of SER a of the parasite receptor the vertebrate of the in cells SER of the canine receptor in epithelial cells the receptor in in that the of SER in was of the of that of the receptor the that a growth factor receptor able the vertebrate The that the SER was the of the and have the of a mansoni of the growth factor receptor a in growth factor in was a of growth factor with a functional of the receptor the receptor Mol. Biochem. Parasitol. with the receptor the the of in and the that development with parasite performed in the of mansoni in the of of and the of and The have been with that in C. C. C. C. Parasitol. in work that and in with of assays performed indicated that in that in and the The that SER was in Mol. Biochem. Parasitol. a in with the of SER the the that SER in a the and previously Mol. Biochem. Parasitol. in the of that was able in with a of the of indicated the that the SER molecule was parasite and and in the of in the of the receptor vertebrate and a vertebrate the of the role of in in the of a of SER an important role in development and an of the of SER and with EGF-R the of that and the and L. and with the EGF-R and the