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Molecular Mechanisms of Signalling and Membrane Transport pp 197–209Cite as

Receptor Regulation of Phospholipases C and D

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Part of the book series: NATO ASI Series ((ASIH,volume 101))

Abstract

A large variety of hormones, neurotransmitters and growth factors regulate cellular functions by stimulating phospholipase C (PLC) enzymes (Berridge, 1993; Divecha & Irvine, 1995; Exton, 1996). These phospholipases hydrolyze phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], a rare and uniquely polar plasma membrane phospholipid, generating the two second messengers, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol. InsP3 exerts its effect by binding to specific receptors located on components of the endoplasmatic reticulum, thereby leading to a quantal release of calcium (Clapham, 1995). The accumulation of diacylglycerol in the plasma membrane due to the hydrolysis of PtdIns(4,5)P2 induces the translocation of certain protein kinase C (PKC) isozymes from the cytosol to the membrane and their concurrent activation (Nishizuka, 1995). The classical or conventional PKC isozymes (α, βl, β2, and γ) possess C1 and C2 domains, binding diacylglycerol or phorbol ester and calcium, respectively, and are thus calcium-dependent, whereas the other isoforms (δ, ε, η, θ) lack the C2 domain and are therefore calcium-independent. The atypical PKC isozymes ζ and λ are not only calcium-independent, but also diacylglycerol- or phorbol esterindependent, due to deletions or differences in the C1 domain. However, these enzymes are still dependent upon phosphatidylserine and are activated by other lipids (Nishizuka, 1995). The increase in cytoplasmic calcium and activation of different PKC isozymes initiated by PLC-catalyzed hydrolysis of PtdIns(4,5)P2 apparently participate in the transduction of mitogenic signals across the plasma membrane into the nucleus leading to cell growth and cell transformation (Berridge, 1993; Nishizuka, 1995).

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Authors and Affiliations

  1. Institut für Pharmakologie, Universität GH Essen, D-45122, Essen, Germany

    Martina Schmidt, Ulrich Rümenapp, Chunyi Zhang, Jutta Keller, Barbara Lohmann & Karl H. Jakobs

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  1. Martina Schmidt
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  2. Ulrich Rümenapp
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  3. Chunyi Zhang
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  4. Jutta Keller
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  5. Barbara Lohmann
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  6. Karl H. Jakobs
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  1. Centre for Biomembranes and Lipid Enzymology, Utrecht University, Padualaan 8, 3584 TB, Utrecht, The Netherlands

    Karel W. A. Wirtz

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Schmidt, M., Rümenapp, U., Zhang, C., Keller, J., Lohmann, B., Jakobs, K.H. (1997). Receptor Regulation of Phospholipases C and D. In: Wirtz, K.W.A. (eds) Molecular Mechanisms of Signalling and Membrane Transport. NATO ASI Series, vol 101. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60799-8_14

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