Calcium is the switch in the moonlighting dual function of the ligand-activated receptor kinase phytosulfokine receptor 1

Victor Muleya, Janet Wheeler, Oziniel Ruzvidzo, Lubna Freihat, David Thomas Manallack, Christoph Andreas Gehring, Helen Ruth Irving

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

Background: A number of receptor kinases contain guanylate cyclase (GC) catalytic centres encapsulated in the cytosolic kinase domain. A prototypical example is the phytosulfokine receptor 1 (PSKR1) that is involved in regulating growth responses in plants. PSKR1 contains both kinase and GC activities however the underlying mechanisms regulating the dual functions have remained elusive. Findings: Here, we confirm the dual activity of the cytoplasmic domain of the PSKR1 receptor. We show that mutations within the guanylate cyclase centre modulate the GC activity while not affecting the kinase catalytic activity. Using physiologically relevant Ca2+ levels, we demonstrate that its GC activity is enhanced over two-fold by Ca2+ in a concentration-dependent manner. Conversely, increasing Ca2+ levels inhibits kinase activity up to 500-fold at 100 nM Ca2+. Conclusions: Changes in calcium at physiological levels can regulate the kinase and GC activities of PSKR1. We therefore propose a functional model of how calcium acts as a bimodal switch between kinase and GC activity in PSKR1 that could be relevant to other members of this novel class of ligand-activated receptor kinases.
Original languageEnglish
Article number60
Pages (from-to)1 - 5
Number of pages5
JournalCell Communication and Signaling
Volume12
DOIs
Publication statusPublished - 2014

Cite this

Muleya, Victor ; Wheeler, Janet ; Ruzvidzo, Oziniel ; Freihat, Lubna ; Manallack, David Thomas ; Gehring, Christoph Andreas ; Irving, Helen Ruth. / Calcium is the switch in the moonlighting dual function of the ligand-activated receptor kinase phytosulfokine receptor 1. In: Cell Communication and Signaling. 2014 ; Vol. 12. pp. 1 - 5.
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abstract = "Background: A number of receptor kinases contain guanylate cyclase (GC) catalytic centres encapsulated in the cytosolic kinase domain. A prototypical example is the phytosulfokine receptor 1 (PSKR1) that is involved in regulating growth responses in plants. PSKR1 contains both kinase and GC activities however the underlying mechanisms regulating the dual functions have remained elusive. Findings: Here, we confirm the dual activity of the cytoplasmic domain of the PSKR1 receptor. We show that mutations within the guanylate cyclase centre modulate the GC activity while not affecting the kinase catalytic activity. Using physiologically relevant Ca2+ levels, we demonstrate that its GC activity is enhanced over two-fold by Ca2+ in a concentration-dependent manner. Conversely, increasing Ca2+ levels inhibits kinase activity up to 500-fold at 100 nM Ca2+. Conclusions: Changes in calcium at physiological levels can regulate the kinase and GC activities of PSKR1. We therefore propose a functional model of how calcium acts as a bimodal switch between kinase and GC activity in PSKR1 that could be relevant to other members of this novel class of ligand-activated receptor kinases.",
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Calcium is the switch in the moonlighting dual function of the ligand-activated receptor kinase phytosulfokine receptor 1. / Muleya, Victor; Wheeler, Janet; Ruzvidzo, Oziniel; Freihat, Lubna; Manallack, David Thomas; Gehring, Christoph Andreas; Irving, Helen Ruth.

In: Cell Communication and Signaling, Vol. 12, 60, 2014, p. 1 - 5.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Manallack, David Thomas

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AU - Irving, Helen Ruth

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