Activation of phospholipase C by heat shock requires GTP analogs and is resistant to pertussis toxin.
The heat shock response in mammals consists of a complex array of intracellular reactions initiated by stress, although its regulation is poorly understood. We have investigated the role of transmembrane signal transduction in the response, examining mechanisms involved in the activation of phospholipase C (PLC) by heat shock. In rodent fibroblasts permeabilized with digitonin, heat shock and receptor-mediated PLC activity exhibited a strict GTP analog dependency. This indicates that heat shock-mediated phospholipase activation, in common with receptor mediated stimulation, does not involve direct effects on the phospholipases and suggests the participation of GTP binding (G) proteins in the activation process. When cells were treated with the inhibitor pertussis toxin (PTX), the phospholipases retained their inducibility by heat shock, but became refractory to thrombin treatment, indicating that heat shock may influence PLC activity through a distinct population of G proteins compared to thrombin. The data seem to exclude a role for PTX sensitive G proteins in the production of IP3 after heating and suggest a pathway involving the direct thermal activation of the Gq class of G proteins, which are coupled to the PLC beta 1 isoform.
Calderwood
S K
SK
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Stevenson
M A
MA
Price
B D
BD
D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051379:Mice; D037342:Pertussis Toxin; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D013917:Thrombin; D019204:GTP-Binding Proteins