Peer-Reviewed Journal Details
Mandatory Fields
O'Donovan, HC;Kiely, PA;O'Connor, R
2007
December
Cellular Signalling
Effects of RACK1 on cell migration and IGF-I signalling in cardiomyoctes are not dependent on an association with the IGF-IR
Validated
WOS: 15 ()
Optional Fields
PROTEIN-KINASE-C GROWTH-FACTOR-I RECEPTOR-INTERACTING PROTEIN CULTURED CARDIAC MYOCYTES BETA-SUBUNIT PHOSPHODIESTERASE PDE4D5 SCAFFOLD PROTEIN INSULIN EPSILON APOPTOSIS
19
2588
2595
RACK1 can act as a scaffolding protein to integrate IGF-IR and integrin signalling in transformed cells but its actions in regulating IGF-IR signalling in non-transformed cells are less well understood. Here, we investigated the function of RACK1 in the non-transformed cardiomyocyte cell line H9c2. Overexpression of RACK1 in H9c2 cells was sufficient to increase cell size, increase adhesion to collagen 1, enhance protection from hydrogen peroxide-induced cell death, and increase cell migration. However, cell proliferation was decreased in these cells. Small interfering RNA (siRNA)mediated suppression of RACK I in H9c2 cells resulted in decreased cell adhesion and migration, but had no effect on cell proliferation or size. Increased basal and IGF-I-mediated Erk phosphorylation was observed in RACK I-overexpressing H9c2 cells. Interestingly, contrary to observations in transformed cells. RACK1 was not observed to interact with the IGF-IR in H9c2 cells. Also in contrast to observations in transformed cells, IGF-I promoted recruitment of Src to RACK1 as well as recruitment of PKC alpha, and PKC epsilon to RACK1. Overall, the data indicate that in H9c2 cells RACK1 can influence cell size, cell survival, adhesion, migration, but its responses to IGF-I are independent of an association with the IGF-IR. Thus, the composition of the RACK1 scaffolding complex and its effects on IGF-I signalling may be different in transformed and non-transformed cells. (C) 2007 Elsevier Inc. All rights reserved.
NEW YORK
0898-6568
10.1016/j.cellsig.2007.08.010
Grant Details