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Heat Shock Proteins in Signaling Pathways pp 161–182Cite as

Role of Heat Shock Protein 90 in Regulating Downstream Signal Transduction Cascades

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Part of the book series: Heat Shock Proteins ((HESP,volume 17))

Abstract

Heat shock protein 90 (Hsp90) regulates a broad swathe of proteins critical for normal and pathological cell function. One major class of regulated proteins are signal transduction molecules, such as the Mitogen Activated Protein Kinases (MAPK), G Protein Coupled Receptor (GPCR) regulatory kinases, and similar. Hsp90 regulates these signaling proteins by promoting proper folding and protein stability, however, Hsp90 also regulates signaling activation and association/targeting of mature proteins during the course of acute signal transduction. As these signaling proteins are ubiquitously expressed in most cells and are downstream of numerous different receptor systems, Hsp90 regulation of signaling proteins is strongly and broadly impactful. In this chapter, we will discuss the main themes of signaling protein regulation by Hsp90, and highlight several crucial signaling protein families. We will discuss the impact of Hsp90 on signaling downstream of multiple receptor systems, and subsequent effects on physiology and pathophysiology. We will also suggest means to manipulate these regulatory relationships to improve clinical therapy, and future directions for the field of Hsp90 signaling regulation.

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Abbreviations

AMPK:

adenosine monophosphate-activated protein kinase

CDK:

cyclin-dependent kinase

eNOS:

endothelial nitric oxide synthase

ERK:

extracellular signal-regulated kinase

FAK:

focal adhesion kinase

GPCR:

G protein coupled receptor

GRK:

G protein-coupled receptor kinases

GSK-3:

glycogen synthase kinase-3

Hsp90:

heat shock protein 90

IKK:

IκB kinase

JNK:

c-Jun N-terminal kinase

MAPK:

mitogen activated protein kinase

MOR:

Mu opioid receptor

PKA:

protein kinase A

PKC:

protein kinase C

RTK:

receptor tyrosine kinases

VEGFR:

vascular endothelial growth factor receptor

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Acknowledgements

We would like to acknowledge institutional support from the University of Arizona. We would also like to acknowledge our collaborator Dr. Brian Blagg from the University of Notre Dame for collaboration and valuable discussion on Hsp90 that contributed to the background of this work.

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  1. Authors Wei Lei, David Duron and Carrie Stine have equally contributed to this chapter.

Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA

    Wei Lei, David Duron, Carrie Stine & John M. Streicher

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  1. Wei Lei
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  2. David Duron
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  3. Carrie Stine
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  4. John M. Streicher
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Correspondence to John M. Streicher .

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Editors and Affiliations

  1. Professor, Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Lei, W., Duron, D., Stine, C., Streicher, J.M. (2019). Role of Heat Shock Protein 90 in Regulating Downstream Signal Transduction Cascades. In: Asea, A., Kaur, P. (eds) Heat Shock Proteins in Signaling Pathways. Heat Shock Proteins, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-030-03952-3_9

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