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Am J Physiol Cell Physiol 283: C327-C337, 2002. First published February 27, 2002; doi:10.1152/ajpcell.00442.2001
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Vol. 283, Issue 1, C327-C337, July 2002

TIMAP, a novel CAAX box protein regulated by TGF-beta 1 and expressed in endothelial cells

Wangsen Cao1, Subhendra N. Mattagajasingh2, Hangxue Xu1, Kwanghee Kim2, Wolfgang Fierlbeck2, Jie Deng1, Charles J. Lowenstein1, and Barbara J. Ballermann2

1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; and 2 Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461

Representational difference analysis of the glomerular endothelial cell response to transforming growth factor-beta 1 (TGF-beta 1) revealed a novel gene, TIMAP (TGF-beta -inhibited membrane-associated protein), which contains 10 exons and maps to human chromosome 20.q11.22. By Northern blot, TIMAP mRNA is highly expressed in all cultured endothelial and hematopoietic cells. The frequency of the TIMAP SAGE tag is much greater in endothelial cell SAGE databases than in nonendothelial cells. Immunofluorescence studies of rat tissues show that anti-TIMAP antibodies localize to vascular endothelium. TGF-beta 1 represses TIMAP through a protein synthesis- and histone deacetylase-dependent process. The TIMAP protein contains five ankyrin repeats, a protein phosphatase-1 (PP1)-interacting domain, a COOH-terminal CAAX box, a domain arrangement similar to that of MYPT3, and a PP1 inhibitor. A green fluorescent protein-TIMAP fusion protein localized to the plasma membrane in a CAAX box-dependent fashion. Hence, TIMAP is a novel gene highly expressed in endothelial and hematopoietic cells and regulated by TGF-beta 1. On the basis of its domain structure, TIMAP may serve a signaling function, potentially through interaction with PP1.

hematopoietic cells; rat; representational difference analysis; glomerular endothelial cells; human; vascular endothelial cells


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