Intramolecular Crosstalk between Catalytic Activities of Receptor Kinases
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/627011
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AbstractSignal modulation is important for the growth and development of plants and this process is mediated by a number of factors including physiological growth regulators and their associated signal transduction pathways. Protein kinases play a central role in signaling, including those involving pathogen response mechanisms. We previously demonstrated an active guanylate cyclase (GC) catalytic center in the brassinosteroid insensitive receptor (AtBRI1) within an active intracellular kinase domain resulting in dual enzymatic activity. Here we propose a novel type of receptor architecture that is characterized by a functional GC catalytic center nested in the cytosolic kinase domain enabling intramolecular crosstalk. This may be through a cGMP-AtBRI1 complex forming that may induce a negative feedback mechanism leading to desensitisation of the receptor, regulated through the cGMP production pathway. We further argue that the comparatively low but highly localized cGMP generated by the GC in response to a ligand is sufficient to modulate the kinase activity. This type of receptor therefore provides a molecular switch that directly and/or indirectly affects ligand dependent phosphorylation of downstream signaling cascades and suggests that subsequent signal transduction and modulation works in conjunction with the kinase in downstream signaling.
CitationKwezi L, Wheeler JI, Marondedze C, Gehring C, Irving HR (2018) Intramolecular Crosstalk between Catalytic Activities of Receptor Kinases. Plant Signaling & Behavior: 00–00. Available: http://dx.doi.org/10.1080/15592324.2018.1430544.
SponsorsFunding for this research was provided by the Australian Research Council's Discovery funding scheme (project numbers DP0878194 and DP110104164) and the National Research Foundation South Africa (grant numbers 78843; IRF2009021800047).
PublisherInforma UK Limited
JournalPlant Signaling & Behavior
- The phytosulfokine (PSK) receptor is capable of guanylate cyclase activity and enabling cyclic GMP-dependent signaling in plants.
- Authors: Kwezi L, Ruzvidzo O, Wheeler JI, Govender K, Iacuone S, Thompson PE, Gehring C, Irving HR
- Issue date: 2011 Jun 24
- The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling.
- Authors: Wheeler JI, Wong A, Marondedze C, Groen AJ, Kwezi L, Freihat L, Vyas J, Raji MA, Irving HR, Gehring C
- Issue date: 2017 Aug
- Calcium is the switch in the moonlighting dual function of the ligand-activated receptor kinase phytosulfokine receptor 1.
- Authors: Muleya V, Wheeler JI, Ruzvidzo O, Freihat L, Manallack DT, Gehring C, Irving HR
- Issue date: 2014 Sep 23
- Moonlighting kinases with guanylate cyclase activity can tune regulatory signal networks.
- Authors: Irving HR, Kwezi L, Wheeler J, Gehring C
- Issue date: 2012 Feb
- Phosphorylation of the dimeric cytoplasmic domain of the phytosulfokine receptor, PSKR1.
- Authors: Muleya V, Marondedze C, Wheeler JI, Thomas L, Mok YF, Griffin MD, Manallack DT, Kwezi L, Lilley KS, Gehring C, Irving HR
- Issue date: 2016 Oct 1
Showing items related by title, author, creator and subject.
Calcium is the switch in the moonlighting dual function of the ligand-activated receptor kinase phytosulfokine receptor 1Muleya, Victor; Wheeler, Janet I; Ruzvidzo, Oziniel; Freihat, Lubna; Manallack, David T; Gehring, Christoph A; Irving, Helen R (Cell Communication and Signaling, Springer Nature, 2014-09-23) [Article]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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Advisor: Habuchi, Satoshi
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17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.Ren, Jian; Wang, Xuhui; Wang, Guangchao; Wu, Junhua (Bone, Elsevier BV, 2013-04) [Article]Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17β estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ERα/β) by fulvestrant and ERα knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ERα/β pathway, and sensitized osteocytes to mechanical loading. © 2012 Elsevier Inc. All rights reserved.