α1-Adrenergic Receptor Subtypes Differentially Control the Cell Cycle of Transfected CHO Cells through a cAMP-dependent Mechanism Involving p27 Kip1

• Published in: The Journal of biological chemistry 2003-01, Vol.278 (1), p.672
• Main Authors: Katsushi Shibata, Susumu Katsuma, Takaaki Koshimizu, Hitomi Shinoura, Akira Hirasawa, Akito Tanoue, Gozoh Tsujimoto
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M201375200

Three distinct subtypes of α 1 -adrenergic receptors (α 1 A-, α 1 B-, and α 1 D-AR) play a prominent role in cell growth. However, little is known about subtype-specific effects on cell proliferation. The activation of α 1 A- or α 1 B-AR inhibits serum-promoted cell proliferation, whereas α 1 D-AR activation does not show such an inhibitory effect. Notably, cell-cycle progression was blocked at G 1 /S transition after activation of α 1 A/α 1 B-AR but not of α 1 D-AR. In agreement with the differential cell proliferation effect, cAMP production was increased after activation of α 1 A/α 1 B-AR but not α 1 D-AR, whereas all α 1 -AR subtypes are associated with inositol 1,4,5-trisphosphate production and mitogen-activated protein kinase activation in a similar fashion. Furthermore, the serum-induced reduction in the levels of the cyclin-dependent kinase inhibitor, p27 Kip1 , was blocked after activation of α 1 A/α 1 B-AR but not α 1 D-AR. These results show that α 1 -AR subtypes differentially activate the cAMP/p27 Kip1 pathway and thereby have differential inhibitory effects on cell proliferation. Subtype-dependent effects should be taken into consideration when assessing the physiological response of native cells where α 1 -AR subtypes are generally co-expressed.