4.2 Article Proceedings Paper

Tyrosine kinase and cooperative TGFβ signaling in the reproductive organs of Schistosoma mansoni

Journal

EXPERIMENTAL PARASITOLOGY
Volume 117, Issue 3, Pages 318-336

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.exppara.2007.04.006

Keywords

BrdU, bromodeoxyuridine; Csk, C-terminal Src kinase; CTK, cytoplasmatic tyrosine kinase; DAPI, 4',6-diamidino-2-phenylindol; DNA, deoxyribonucleic acid; DRF, diaphanous-related formin; ECM, extracellular matrix; EGF(R), epidermal growth factor (receptor); Erk, extracellular signal-regulated kinase; EST, expressed sequence tag; FAK, focal adhesion kinase; FH1 domain, formin homology 1 domain; FKBP12, FK506 binding protein 12; GABA, gamma-aminobutyric acid; GAP, GTPase-activating proteins; GEF, guanine-nucleotide exchange factor; GPCR, G protein-coupled receptor; GDP, guanosine diphosphate; GTP, guanosine triphosphate; IR, insulin receptor; MAPK, mitogen-activated protein kinase; MEK, Erk-kinase; ORF, open reading frame; PTK, protein tyrosine kinase; RTK, receptor tyrosine kinase; RT-PCR, reverse transcriptase polymerase chain reaction; RXR, retinoid X receptor; SH2/3/4, Src-homology domain 2/3/4; S. mansoni, Schistosoma mansoni; SmGCP, Schistosoma mansoni gynaecophoric canal protein; SmDRF, Schistosoma mansoni diaphanous-related formin; SRE, serum response element; SRF, serum response factor; T beta RI/II, transmembrane serine/threonine kinase type I/II receptor; TGF beta, transforming growth factor beta; TRIKI, TGF beta RI kinase inhibitor; TK (domain), tyrosine kinase (domain); VFT, venus flytrap; Schistosoma mansoni; male-female interaction; vitellarium/vitellocyte; ovary/oocyte; female reproductive activity; tyrosine kinase; Src; Syk; TGF beta; nuclear receptor; schistosomiasis; drug target; kinase inhibitors

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Drug-induced suppression of female schistosome sexual maturation is an auspicious strategy to combat schistosomiasis since the eggs are the causative agent. The establishment of drug targets requires knowledge about the molecular mechanisms that regulate the development of the female reproductive organs, which include vitellarium and ovary. This review summarizes recent studies suggesting tyrosine kinases as important factors for the regulation of female gonad development. In this context, especially cytoplasmatic tyrosine kinases of the Src class seem to play dominant roles. Moreover, experimental data and theoretical concepts are provided supporting a crosstalk between tyrosine kinase and TGF beta signaling in the production of vitellocytes. Finally, we take advantage from the schistosome genome project to propose a model for the regulation of vitelline-cell production and differentiation. (C) 2007 Elsevier Inc. All rights reserved.

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