Current topics in cellular regulation / 31 by Bernard L. Horecker, Earl R. Stadtman, P. Boon Chock

By Bernard L. Horecker, Earl R. Stadtman, P. Boon Chock

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However, this is not always the case. In particular, PKC translocation 2+ can occur under conditions in which no increase in C a influx rate occurs. This translocated PKC can then persist in the membrane for a period of time after removal of the signal responsible for its initial translocation. When a subsequent extracellular messenger acts to in2+ crease C a influx rate, this persistently translocated PKC is immediately activated. Hence, certain extracellular messengers can, by causing persistent PKC translocation, induce a time-dependent change in cell responsiveness.

2 + During the sustained phase of the response, a change in [ C a ] s m oc2+ curs as a result of an agonist-induced increase in C a influx rate. The 2 + increase in [ C a ] s m activates PM-associated protein kinase C (and other PM-associated transducers). The activated protein kinase C catalyzes the phosphorylation of another subset of cellular proteins responsible for mediating the sustained phase of the response. It seems likely t h a t not all of the proteins t h a t display an increase in extent of phosphorylation during this phase of the response are direct substrates for PKC, but rather they are substrates for other specific protein kinases t h a t are components of a protein kinase cascade whose sequential activation begins with protein kinase C.

RASMUSSEN TIME (min) FIG. 12. Models of the regulation of aldosterone secretion by angiotensin II. 0 mM extracellular K . 0 mM extracellular Κ . Note that even though Ang II-receptor interaction leads, in both cases, to the activation of Pi-specific phospholipase C (PI-PLC) and the generation of both inositol 1,4,5-trisphosphate (ΙΡ3) and diacylglycerol (DAG), the aldosterone secretory responses are different. 5 mM K , a sustained response is seen (A). In both cases, the rise in IP 3 content leads to a release of intracellular 2+ 2+ 2+ C a and a rise in the C a concentration in the cell cytosol, [ C a ] c , the phosphoryla- CALCIUM AS INTRACELLULAR MESSENGER 51 B TIME (min) + tion of initial phase proteins ( P r aP ) , and a rapid initial secretory response.

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