Regulation of auxin transport polarity by AGC kinases

The plant hormone auxin controls plant development through gradients and maxima that are generated by PIN efflux carrier driven polar auxin transport. PIN proteins direct this cell-to-cell auxin transport, and thus orient plant development through their asymmetric subcellular distribution. PIN polarity is regulated by PINOID and the phototropins, members of the AGC protein serine/threonine kinase family. Here we review the signaling pathways of these kinases and the role of calcium and BTB proteins in translating both internal and external signals into developmental responses via PIN relocalization, to adapt plant development to changing environmental conditions.     

Mammalian TOR signaling to the AGC kinases

The mechanistic (or mammalian) target of rapamycin (mTOR), an evolutionarily conserved protein kinase, orchestrates cellular responses to growth, metabolic and stress signals. mTOR processes various extracellular and intracellular inputs as part of two mTOR protein complexes, mTORC1 or mTORC2. The mTORCs have numerous cellular targets but members of a family of protein kinases, the protein kinase (PK)A/PKG/PKC (AGC) family are the best characterized direct mTOR substrates. The AGC kinases control multiple cellular functions and deregulation of many members of this family underlies numerous pathological conditions. mTOR phosphorylates conserved motifs in these kinases to allosterically augment their activity, influence substrate specificity, and promote protein maturation and stability. Activation of AGC kinases in turn triggers the phosphorylation of diverse, often overlapping, targets that ultimately control cellular response to a wide spectrum of stimuli. This review will highlight recent findings on how mTOR regulates AGC kinases and how mTOR activity is feedback regulated by these kinases. We will discuss how this regulation can modulate downstream targets in the mTOR pathway that could account for the varied cellular functions of mTOR.     

Mammalian TOR signaling to the AGC kinases

The mechanistic (or mammalian) target of rapamycin (mTOR), an evolutionarily conserved protein kinase, orchestrates cellular responses to growth, metabolic and stress signals. mTOR processes various extracellular and intracellular inputs as part of two mTOR protein complexes, mTORC1 or mTORC2. The mTORCs have numerous cellular targets but members of a family of protein kinases, the protein kinase (PK)A/PKG/PKC (AGC) family are the best characterized direct mTOR substrates. The AGC kinases control multiple cellular functions and deregulation of many members of this family underlies numerous pathological conditions. mTOR phosphorylates conserved motifs in these kinases to allosterically augment their activity, influence substrate specificity, and promote protein maturation and stability. Activation of AGC kinases in turn triggers the phosphorylation of diverse, often overlapping, targets that ultimately control cellular response to a wide spectrum of stimuli. This review will highlight recent findings on how mTOR regulates AGC kinases and how mTOR activity is feedback regulated by these kinases. We will discuss how this regulation can modulate downstream targets in the mTOR pathway that could account for the varied cellular functions of mTOR.     

Plant development: auxin in loops

Concentration gradients of the hormone auxin are associated with various patterning events in plants. Recent work has refined our picture of the complex and dynamic system of auxin transport underlying the formation of these gradients.     

AGC kinases in plant development and defense

More than 100,000 publications demonstrate that AGC kinases are important regulators of growth, metabolism, proliferation, cell divison, survival and apoptosis in mammalian systems.¹ Mutation and/or dysregulation of these kinases contribute to the pathogenesis of many human diseases, including cancer and diabetes. Although AGC kinases are also present in plants, little is known about their functions. We demonstrated that the AGC kinase OXIDATIVE SIGNAL-INDUCIBLE1 (OXI1/AGC2-1) regulate important developmental processes and defense responses in plants. The summary of recent progress also demonstrates that we are only beginning to understand the role of this kinase pathway in plants.Key words: AGC kinases, reactive oxygen species, plant stress, plant microbe interaction, plant pathogen     

Plant signalling: the inexorable rise of auxin

The flow of signalling molecules across a field of cells to generate a pattern that is then transduced into a differential response in those cells is a fundamental concept in developmental biology. Recent studies have identified a system that regulates the flux of the growth factor auxin through plant tissues via the subcellular asymmetric localization of specific transporters. The recurrent use of this auxin transport system in different developmental and physiological contexts reveals a fundamental mechanism underpinning organogenesis, stem cell positioning and the growth response of the plant to the environment. Here, I will discuss key advances in the identification of auxin transporters and their integration with auxin signal transduction pathways.     

Unraveling the evolution of auxin signaling

Auxin signaling is central to plant growth and development, yet hardly anything is known about its evolutionary origin. While the presence of key players in auxin signaling has been analyzed in various land plant species, similar analyses in the green algal lineages are lacking. Here, we survey the key players in auxin biology in the available genomes of Chlorophyta species. We found that the genetic potential for auxin biosynthesis and AUXIN1 (AUX1)/LIKE AUX1- and P-GLYCOPROTEIN/ATP-BINDING CASSETTE subfamily B-dependent transport is already present in several single-celled and colony-forming Chlorophyta species. In addition, our analysis of expressed sequence tag libraries from Coleochaete orbicularis and Spirogyra pratensis, green algae of the Streptophyta clade that are evolutionarily closer to the land plants than those of the Chlorophyta clade, revealed the presence of partial AUXIN RESPONSE FACTORs and/or AUXIN/INDOLE-3-ACETIC ACID proteins (the key factors in auxin signaling) and PIN-FORMED-like proteins (the best-characterized auxin-efflux carriers). While the identification of these possible AUXIN RESPONSE FACTOR- and AUXIN/INDOLE-3-ACETIC ACID precursors and putative PIN-FORMED orthologs calls for a deeper investigation of their evolution after sequencing more intermediate genomes, it emphasizes that the canonical auxin response machinery and auxin transport mechanisms were, at least in part, already present before plants "moved" to land habitats.     

Plant hormones: the interplay of brassinosteroids and auxin

Interplay between hormones is crucial for the coordination of plant development. Recent work has provided important new insights into the close relationship between brassinosteroid and auxin signalling pathways in plants.     

Protein tyrosine kinases Src and Csk: a tail's tale

Csk and Src are two protein tyrosine kinases with similar amino acid sequences but very different structures and functions. Csk catalyzes a tail phosphorylation reaction on Src and thereby restrains Src's activity and oncogenic potential. Comparative analysis of the domain interactions in these enzymes provides a lesson in signalling diversity and mechanisms of enzyme regulation. The molecular basis of the specificity of Csk targeting the Src tail appears to involve both local and long-range interactions and illustrates the complexity of selective targeting in post-translational modification.     

Growth signalling pathways in Arabidopsis and the AGC protein kinases

Lipid-derived signals are central to regulating a multitude of cellular processes but, in plants, little is known of the downstream signalling pathways. The Arabidopsis 3-phosphoinositide-dependent protein kinase (PDK1) could couple lipid signals to the activation of several protein kinases of the so-called AGC kinase family. The Arabidopsis AGC kinases contain sequence motives required for the docking of PDK1 and phosphorylation of their activation loop in the kinase catalytic domain. It is becoming evident that specific members of the AGC kinases are implicated in key growth signalling pathways. For example, Arabidopsis p70(S6K) might be a nodal point able to integrate hormonal and developmental signals with nutritional inputs, together with the Arabidopsis Target of Rapamycin (TOR) protein.     

Plant receptor kinases

Recent plant genome analyses have revealed a large number of genes encoding receptor-like kinases (RLKs) in plants. Theyare transmembrane proteins structurally related to the animal tyrosine and serin/threonine families with differences in their extracellular domains. There are more than 20 classes of plant RLKs, distinguished according to their extracellular domains, which can potentially bind an array of molecules. Although the majority of these RLKs remains uncharacterized, several members of this family are known to function in a diverse biological processes including plant growth and development, self-incompatibility, hormone perception and plant-microbe interactions. Despite knowledge of RLKs functions is increasing rapidly, yet major challenges remain. These include identifying ligands that activate RLKs and characterizing downstream pathways.     

TOR regulation of AGC kinases in yeast and mammals

The TOR (target of rapamycin), an atypical protein kinase, is evolutionarily conserved from yeast to man. Pharmacological studies using rapamycin to inhibit TOR and yeast genetic studies have provided key insights on the function of TOR in growth regulation. One of the first bona fide cellular targets of TOR was the mammalian protein kinase p70 S6K (p70 S6 kinase), a member of a family of kinases called AGC (protein kinase A/protein kinase G/protein kinase C-family) kinases, which include PKA (cAMP-dependent protein kinase A), PKG (cGMP-dependent kinase) and PKC (protein kinase C). AGC kinases are also highly conserved and play a myriad of roles in cellular growth, proliferation and survival. The AGC kinases are regulated by a common scheme that involves phosphorylation of the kinase activation loop by PDK1 (phosphoinositide-dependent kinase 1), and phosphorylation at one or more sites at the C-terminal tail. The identification of two distinct TOR protein complexes, TORC1 (TOR complex 1) and TORC2, with different sensitivities to rapamycin, revealed that TOR, as part of either complex, can mediate phosphorylation at the C-terminal tail for optimal activation of a number of AGC kinases. Together, these studies elucidated that a fundamental function of TOR conserved throughout evolution may be to balance growth versus survival signals by regulating AGC kinases in response to nutrients and environmental conditions. This present review highlights this emerging function of TOR that is conserved from budding and fission yeast to mammals.     

Plant hormones: Ins and outs of auxin transport

Regulated transport has long been known to play a key part in action of the plant hormone auxin. Now, at last, a family of auxin efflux carriers has been identified, and the characterisation of one family member has provided strong evidence in support of models that have been proposed to explain gravitropic curvature in roots.     

Plant tropisms: The ins and outs of auxin

The Cholodny–Went hypothesis holds that gravitropic curvature of a growing plant organ depends on regulated transport of the plant hormone auxin; new studies of the agravitropic mutant aux1 of Arabidopsis provide strong evidence in support of this hypothesis.     

Plant roots: recycled auxin energizes patterning and growth

Recent studies show that, in plant roots, mutually dependent regulatory mechanisms operating at cell and tissue levels interact to generate a self-sustaining distribution of the hormone auxin which provides a framework for developmental patterning and growth.