G proteins in signal transduction: the regulation of phospholipase C.

P. C. Sternweis, A. V. Smrcka

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The hydrolysis of phosphatidylinositol 4,5-bisphosphate by specific phospholipase C (PLC) enzymes produces two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) of the Gq subfamily activate the PLC beta 1 isoform of PLC. We have purified three isozymes of PLC beta: PLC beta 1 and PLC beta 3 from rat brain and PLC beta 2 from HL-60 cells. Whereas the beta 1 and beta 2 isozymes appear restricted to a few cell types, beta 3 is broadly distributed. Gq alpha (the alpha subunit of the Gq subfamily) can activate all three isoforms but PLC beta 2 is much less sensitive. Thus all three enzymes are potential effectors for pertussis toxin-insensitive regulation by hormones. The three beta isozymes can also be activated by purified beta gamma subunits. The PLC beta 3 isoform gives the greatest activation with beta gamma; PLC beta 1 is least responsive. The results indicate that all the known isoforms of mammalian PLC beta can be regulated at unique sites by both Gq alpha and beta gamma subunits. The effect of beta gamma subunits may provide a pathway for the regulation of PLC beta isozymes by pertussis toxin-sensitive G proteins or may indicate that the alpha subunit of Gq and its associated beta gamma both participate in regulation of the same phospholipase molecule.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalCiba Foundation symposium
Volume176
StatePublished - 1993

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Phospholipase C beta
Type C Phospholipases
GTP-Binding Proteins
Signal Transduction
Carrier Proteins
Isoenzymes
Protein Isoforms
Pertussis Toxin
Inositol 1,4,5-Trisphosphate
Phospholipases
HL-60 Cells
Diglycerides
Second Messenger Systems
Enzymes
Phosphatidylinositols
Hydrolysis
Hormones

ASJC Scopus subject areas

  • Medicine(all)

Cite this

G proteins in signal transduction : the regulation of phospholipase C. / Sternweis, P. C.; Smrcka, A. V.

In: Ciba Foundation symposium, Vol. 176, 1993, p. 96-106.

Research output: Contribution to journalArticle

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