TY - JOUR
T1 - The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals
AU - Hou, Rong
AU - Liu, Liming
AU - Anees, Syed
AU - Hiroyasu, Shungo
AU - Sibinga, Nicholas E.S.
PY - 2006/5/8
Y1 - 2006/5/8
N2 - The significance of cadherin superfamily proteins in vascular smooth muscle cell (VSMC) biology is undefined. Here we describe recent studies of the Fat1 protocadherin. Fat1 expression in VSMCs increases significantly after arterial injury or growth factor stimulation. Fat1 knockdown decreases VSMC migration in vitro, but surprisingly, enhances cyclin D1 expression and proliferation. Despite limited similarity to classical cadherins, the Fat1 intracellular domain (Fat1IC) interacts with β-catenin, inhibiting both its nuclear localization and transcriptional activity. Fat1 undergoes cleavage and Fat1 IC species localize to the nucleus; however, inhibition of the cyclin D1 promoter by truncated Fat1IC proteins corresponds to their presence outside the nucleus, which argues against repression of β-catenin-dependent transcription by nuclear Fat1IC. These findings extend recent observations about Fat1 and migration in other cell types, and demonstrate for the first time its antiproliferative activity and interaction with β-catenin. Because it is induced after arterial injury, Fat1 may control VSMC functions central to vascular remodeling by facilitating migration and limiting proliferation.
AB - The significance of cadherin superfamily proteins in vascular smooth muscle cell (VSMC) biology is undefined. Here we describe recent studies of the Fat1 protocadherin. Fat1 expression in VSMCs increases significantly after arterial injury or growth factor stimulation. Fat1 knockdown decreases VSMC migration in vitro, but surprisingly, enhances cyclin D1 expression and proliferation. Despite limited similarity to classical cadherins, the Fat1 intracellular domain (Fat1IC) interacts with β-catenin, inhibiting both its nuclear localization and transcriptional activity. Fat1 undergoes cleavage and Fat1 IC species localize to the nucleus; however, inhibition of the cyclin D1 promoter by truncated Fat1IC proteins corresponds to their presence outside the nucleus, which argues against repression of β-catenin-dependent transcription by nuclear Fat1IC. These findings extend recent observations about Fat1 and migration in other cell types, and demonstrate for the first time its antiproliferative activity and interaction with β-catenin. Because it is induced after arterial injury, Fat1 may control VSMC functions central to vascular remodeling by facilitating migration and limiting proliferation.
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U2 - 10.1083/jcb.200508121
DO - 10.1083/jcb.200508121
M3 - Article
C2 - 16682528
AN - SCOPUS:33646422465
SN - 0021-9525
VL - 173
SP - 417
EP - 429
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 3
ER -