MEDIATION OF GROWTH-FACTOR INDUCED DNA-SYNTHESIS AND CALCIUM MOBILIZATION BY G(Q) AND G(I2)

被引:105
作者
LAMORTE, VJ
HAROOTUNIAN, AT
SPIEGEL, AM
TSIEN, RY
FERAMISCO, JR
机构
[1] UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92093
[2] UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093
[3] UNIV CALIF SAN DIEGO,HOWARD HUGHES INST,LA JOLLA,CA 92093
[4] NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892
关键词
D O I
10.1083/jcb.121.1.91
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A newly identified subclass of the heterotrimeric GTP binding regulatory protein family, G(q), has been found to be expressed in a diverse range of cell types. We investigated the potential role of this protein in growth factor signal transduction pathways and its potential relationship to the function of other Galpha subclasses. Recent biochemical studies have suggested that G(q) regulates the beta 1 isozyme of phospholipase C (PLCbeta1), an effector for some growth factors. By microinjection of inhibitory antibodies specific to distinct G alpha subunits into living cells, we have determined that Galpha(q) transduces bradykinin- and thrombin-stimulated intracellular calcium transients which are likely to be mediated by PLCbeta1. Moreover, we found that Galpha(q) function is required for the mitogenic action of both of these growth factors. These results indicate that both thrombin and bradykinin utilize G(q) to couple to increases in intracellular calcium, and that G(q) is a necessary component of the mitogenic action of these factors. While microinjection of antibodies against Galpha(i2) did not abolish calcium transients stimulated by either of these factors, such microinjection prevented DNA synthesis in response to thrombin but not to bradykinin. These data suggest that thrombin-induced mitogenesis requires both G(q) and G(i2), whereas bradykinin needs only the former. Thus, different growth factors operating upon the same cell type use overlapping yet distinct sets of Galpha subtypes in mitogenic signal transduction pathways. The direct identification of the coupling of both a pertussis toxin sensitive and insensitive G protein subtype in the mitogenic pathways utilized by thrombin offers an in vivo biochemical clarification of previous results obtained by pharmacologic studies.
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页码:91 / 99
页数:9
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