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Transforming growth factor‐β signaling in Anopheles mosquito cells
Author(s) -
Mondal Shankar Prosad,
George Michael,
Luckhart Shirley
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a983-d
Subject(s) - biology , signal transduction , microbiology and biotechnology , anopheles stephensi , smad , phosphorylation , transforming growth factor , kinase , mapk/erk pathway , cell signaling , aedes aegypti , botany , larva
Mammalian transforming growth factor‐β1 (TGF‐β1), ingested through bloodfeeding by malaria vector Anopheles mosquitoes, remains active following ingestion and alters Plasmodium development. The effect of TGF‐β1 is mediated in part by regulation of an inducible Anopheles stephensi nitric oxide synthase (NOS) in the midgut, a key organ for parasite development. In mammals and Drosophila , TGF‐β ligands activate receptor protein serine/threonine kinases (RS/TKs) which phosphorylate cytoplasmic Smads, which translocate into the nucleus to regulate target gene expression. Herein, we characterize aspects of the TGF‐β intracellular signal transduction pathway in Anopheles mosquitoes and describe mammalian TGF‐β1 regulation of mosquito genes. Stimulation of A. stephensi cells with human TGF‐β1 induced Smad phosphorylation, while blockade of TGF‐β signaling by type I RS/TK inhibitor SB431542 reduced NOS expression indicating that signaling by TGF‐β1 is transduced, at least in part, through RS/TK and Smad activation in A. stephensi cells. Moreover, microarray analyses of TGF‐β1‐stimulated Anopheles gambiae cells showed up‐regulation of expression of type I and II TGF‐β receptor (tkv, sax, put) and Smad genes and a variety of other intracellular signal genes including those encoding several mitogen‐activated protein kinases (MAPKs), insulin and Wnt signaling proteins. Our data confirm the existence of a mosquito TGF‐β signaling pathway which is analogous to its vertebrate and Drosophila counterparts and suggest that interaction between Smad and MAPK signaling may be required for efficient antimalarial immune defense. Funding was provided by UCD and NIH (AI50663, C06 RR‐12088‐01).