Publications

If you lack access please contact Joseph Falke to request a reprint.

Selected from 125+ Falke JJ peer-reviewed publications;  Google Scholar citations h-index = 66

  •  (2024) Ras Signaling Mechanisms: New Insights from Single Molecule Biophysics. Biophys J. 123:3277-3280. PMID: 39217418.  doi: 10.1016/j.bpj.2024.08.025.  New & Notable commentary invited by the BJ editors.  Online ahead of print Aug 31, 2024.
  • Anne Marie McCombs, Yohei Ohashi, Joy R. Armendariz, Cory Flavin, Roger L. Williams RL, and Joseph J. Falke (2024) The G-Protein Rab1 Activates VPS34 Complex I, a Class III PI3K, Via both Membrane Recruitment and Allosteric Mechanisms.  In preparation.
  • Kaeden Batz, Marco Ferrier, Ellie Mead, Tim Shih, Ian R. Fleming, Joy R. Amendariz and Joseph J. Falke (2024) Cancer-Linked Ras Mutants with Increased Binding Affinity for the Ras Binding Domain of PI-3-Kinase.  In preparation.
  • PDK1:PKCα heterodimer association-dissociation dynamics in single-molecule diffusion tracks on a target membrane.  Biophysical J.  122(11):2301-2310.  PMID:  36733254.  PMCID:  PMC10257113.  DOI:  10.1016/j.bpj.2023.01.041.  Online ahead of print Feb 2, 2023.
  •  Binding of Active Ras and Its Mutants to the Ras Binding Domain of PI-3-kinase: A Quantitative Approach to KD Measurements.  Analytical Biochem (2023) 663:115019. PMID: 36526022.  DOI:  .  Online ahead of print Dec 18, 2022.
  •  Binding of Active Ras and Its Mutants to the Ras Binding Domain of PI-3-kinase: A Quantitative Approach to KD Measurements.  Analytical Biochem (2023) 663:115019. PMID: 36526022.  DOI:  .  Online ahead of print Dec 18, 2022.
  • PDK1:PKCα heterodimer association-dissociation dynamics in single-molecule diffusion tracks on a target membrane.  Biophysical Journal.
  • Single Molecule Studies Reveal Regulatory Interactions between Master Kinases PDK1, AKT1 and PKC. Biophys J. 2021 Dec 21;120(24):5657-5673. PMID: 34673053. DOI: . (ePub October 19, 2021).  Selected by BJ editors as "New and Notable" article - DOI: .
  •  HPLC Method to Resolve, Identify, and Quantify Guanine Nucleotides Bound to the GTPase Ras. Analytical Biochem 631:114338. PMID: 34433016.  DOI: . (ePub August 22, 2021).
  •  Ras–Guanine Nucleotide Complexes: A UV Spectral Deconvolution Method to Analyze Protein Concentration, Nucleotide Stoichiometry, and Purity.  Analytical Biochem 618:114066. PMID: 33485819.  PMCID: PMC8005285.  DOI: . (ePub April 1, 2021).
  • G. Hayden Swisher, Jonathan P. Hannan, Nicholas J. Cordaro, Annette H. Erbse, and Joseph J. Falke (2020) Ras–Guanine Nucleotide Complexes: A UV Spectral Deconvolution Method to Analyze Protein Concentration, Nucleotide Stoichiometry, and Purity.  Analytical Biochem, In Press 12/11/20.
  • The G-Protein Rab5A Activates VPS34 Complex II, a Class III PI3K, by a Dual Regulatory Mechanism.  Biophys J 119:1-14.  PMID: 33137306.  DOI: 
  • Rapid Exposure of Macrophages to Drugs Resolve Four Classes of Effects on the Leading Edge Sensory Pseudopod:  Non-Perturbing, Adaptive, Disruptive, and Activating.  PLOS ONE 15(5):e0233012.  PMID: 32469878.  PMCID: .  DOI: 
  • Brian P. Ziemba*, Moshe Gordon*, and Joseph J. Falke (2019) Stable Interactions of PDK1 with PKCalpha and AKT1 on a Target Membrane Surface: Single Molecule Analysis, In Preparation.
  • Thomas Buckles, Yohei Ohashi, Shirley Tremel, Roger L. Williams, and Joseph J. Falke (2019) Mechanism of Rab5 Activation of VPS34:  A Single Molecule Study, In Preparation.
  • Brian P. Ziemba*, Thomas Buckles*, and Joseph J. Falke (2019) A Live Cell Assay for Quantifying the Effects of Pharmaceuticals on the Leukocyte Chemosensory Pathway, In Preparation.
  • A PKC-MARCKS-PI3K Regulatory Module Links Ca2+ and PIP3 Signals at the Leading Edge of Polarized Macrophages: A Live Cell Imaging Study. PLoS One 13(5):e0196678. (20 pgs).
  • Single Molecule Analysis Reveals How Receptor and Ras Synergistically Activate PI3K and PIP3 Signaling. Biophysical Journal 113: 2396-2405.
  •  Calmodulin Regulation of a Coupled MARCKS-PI3K Lipid Kinase Circuit: Single Molecule Analysis of a Membrane-Bound Signaling Module. Biochemistry 55: 6395-6405.
  •  Regulation of Phosphoinositide-3-Kinase by PKC and MARCKS: Single Molecule Analysis of a Reconstituted, Membrane-Bound Signaling Pathway. Biophys J 110:1811-25. (Selected ).
  •  Signaling and Sensory Adaptation in E. coli Chemoreceptors:  2015 Update. Trends in Microbiological Sciences 23:257-266.
  •  Architecture and Signal Transduction Mechanism of the Bacterial Chemosensory Array: Progress, Controversies, and Challenges. Curr Opin Struct Biol 29:85-94.
  •  Piston versus Scissors: Chemotaxis Receptors versus Sensor His-Kinase Receptors in Two-Component Signaling Pathways. Structure 22:1219-20.
  •  Increasing and decreasing the ultrastability of bacterial chemotaxis core signaling complexes by modifying protein-protein contacts. Biochemistry. 53:5592-600. Accelerated Publication.
  •  Interactions of Protein Kinase C-alpha C1A and C1B Domains with Membranes: A Combined Computational and Experimental Study. J Am Chem Soc. 136:11757-66.
  •  New insights into bacterial chemoreceptor array structure and assembly from electron cryotomography. Biochemistry 53:1575-85.
  •  Mechanism of Protein Kinase C alpha activation on membrane surfaces: New insights from single molecule analysis. Biochemistry 53:1697-713.
  •  Interplay between phosphoinositide lipids and calcium signals at the leading edge of chemotaxing ameboid cells. Chemistry & Physics of Lipids 182:73-9.
  • Structure, function and on-off switching of a core unit contact between CheA kinase and CheW adaptor protein in the bacterial chemosensory array:  A disulfide mapping and TAM-IDS study. Biochemistry 52:7753-7765.
  •  Molecular mechanism of membrane binding of the GRP1 PH domain. Journal of Molecular Biology 425:3073–3090.
  •  The PH domain of PDK1 exhibits a novel, phospho-regulated monomer-dimer equilibrium with important implications for kinase domain activation: Single molecule and ensemble studies. Biochemistry 52:4820–4829.
  •  The 3.2 Å resolution structure of a Receptor:CheA:CheW signaling complex defines overlapping binding sites and key residue interactions within bacterial chemosensory arrays. Biochemistry 52:3852-65.
  •  Defining a key receptor-CheA kinase contact and elucidating its function in the membrane-bound bacterial chemosensory array: A disulfide mapping and TAM-IDS study. Biochemistry 52:3866-80.
  •  Lateral diffusion of peripheral membrane proteins on supported lipid bilayers is controlled by the additive frictional drags of 1) bound lipids and 2) protein domains penetrating into the bilayer hydrocarbon core. Chemistry and Physics of Lipids 172-173:67-77.
  •  The isolated bacterial chemosensory array possesses quasi- and ultrastable components : Functional links between array stability, cooperativity and order. Biochemistry 51:10218-28.
  •  Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: An EPR site-directed spin labeling and relaxation study. PLoS ONE 7:e33640.
  •  Hydrophobic contributions to the membrane docking of synaptotagmin 7 C2A domain: mechanistic contrast between isoforms 1 and 7. Biochemistry 51:7654-64.
  •  Lipid targeting domain with dual membrane specificity that expands the diversity of intracellular targeting reactions. PNAS 109:1816-17.
  •  Assembly of membrane-bound protein complexes: Detection and analysis by single molecule diffusion. Biochemistry 51:1638-47. (Selected for).
  •  The GRP1 PH domain, like the AKT1 PH domain, possesses a sentry glutamate residue essential for specific targeting to plasma membrane PI(3,4,5)P(3). Biochemistry, 50:9845-56.
  •  Purification of Proteins Using Polyhistidine Affinity Tags. Protein Expression & Purification, 2011 Sep 3.
  •  OS-FRET: A new one-sample method for improved FRET measurements. Biochemistry, 50:451-7.
  •  Lateral diffusion of membrane-bound proteins: A window into protein-lipid interactions. Biophys J, 99:2879-87.(#2 on Biophysical Journal List )
  • Membrane docking geometry and target lipid stoichiometry of membrane-bound PKCa C2 Domain: A combined molecular dynamics and experimental study. J Molecular Biology 402: 301-31.
  •  Evidence that tricyclic small molecules may possess toll-like receptor and myeloid differentiation protein 2 activity. Neuroscience, 168:551-63.
  •  The piston rises again. Structure, 17:1149-51. (Review)
  •  Engineered socket study of signaling through a 4-helix bundle: Evidence for a Yin-Yang mechanism in the kinase control module of the aspartate receptor. Biochemistry, 48:9266-77. (Selected for).
  •  The core signaling proteins of bacterial chemotaxis assemble to form an ultra-stable complex. Biochemistry, 48:6975-87. (Selected for and  (2009)5:541).
  •  Thermal domain motions of CheA kinase in solution: Disulfide trapping reveals the motional constraints leading to trans-autophosphorylation. Biochemistry, 48:3631-44.
  • Single-molecule fluorescence studies of a PH domain: New insights into the membrane docking reaction. Biophysical Journal, 96:566-82.
  • Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav Immun., 24:83-95.
  •  Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of AKT1 PH domain. Biochemistry, 47:12260Ð12269.
  •  Effect of PIP2 binding on the membrane docking geometry of PKC alpha C2 domain: An EPR site-directed spin-labeling and relaxation study. Biochemistry, 47:8301-16.
  •  Bacterial chemoreceptors: High-performance signaling in networked arrays. Trends in Biochemical Sciences, 33:9-19. (Review)
  •  Membrane recruitment as a cancer mechanism: A case study of AKT PH domain. Cellscience Reviews, 4:25-30. (Review)
  •  Structure of the conserved HAMP domain in an intact, membrane-bound chemoreceptor: A disulfide mapping study. Biochemistry (Accelerated), 46:13684-95.
  •  Ca2+ influx is an essential component of the positive feedback loop that maintains leading edge structure and activity in macrophages. PNAS USA, 104:16176-81.
  •  Chemotaxis receptor complexes: from signaling to assembly. PLoS Comput Biol., 3(7):e150.
  •  Use of site-directed cysteine and disulfide chemistry to probe protein structure and dynamics: Applications to soluble and transmembrane receptors of bacterial chemotaxis. Methods in Enzymology, 423:25-51.
  • The PICM chemical scanning method for identifying domain-domain and protein-protein interfaces: Applications to the core signaling complex of bacterial chemotaxis. Methods in Enzymology, 423:1-24.
  • Mechanism of Specific Membrane Targeting by C2 Domains: Localized Pools of Target Lipids Enhance Ca2+ Affinity. Biochemistry 46:4322-36. (Selected as  by Biochemistry Editors).
  • Self-induced docking site of a deeply embedded peripheral membrane protein. Biophysical Journal 92, 517-24. Epub 27 Oct 2006, Pub 15 Jan 2007. (Selected as by Science Editor Gilbert Chin, Science 314 (17), 1050).
  • CheA kinase of bacterial chemotaxis: Chemical mapping of four essential docking sites. Biochemistry (Accelerated Publication) 45, 8699-711.
  • Translocation of protein kinase C alpha to the plasma membrane requires both Ca2+ and PIP2. Molecular Biology of the Cell 17, 56-66.
  • Evidence that the adaptation subdomain of the aspartate receptor is a dynamic four-helix bundle: Cysteine and disulfide scanning studies. Biochemistry 44:12655-66.
  • Conserved glycine residues in the cytoplasmic domain of the aspartate receptor play essential roles in kinase coupling and on-off switching. Biochemistry 44:7687-95.
  • Use of EPR power saturation to analyze the membrane docking geometries of peripheral proteins: Applications to C2 domains. Annual Review of Biophysics and Biomolecular Structure 34:71-90.
  • Adaptation mechanism of the aspartate receptor: Electrostatics of the adaptation subdomain play a key role in modulating kinase activity. Biochemistry 44:1550-1560.
  • Ca2+ activation of the cPLA2 C2 domain: Ordered binding of two Ca2+ ions with positive cooperativity. Biochemistry 43:16320-16328.
  • GRP1 Pleckstrin homology domain: Activation parameters and novel search mechanism for rare target lipid. Biochemistry 43:16161-16173.
  • Corbin, J.A. and J.J. Falke (2004) Affinity tags for protein immobilization and purification. Encyclopedia of Biological Chemistry 1:57-63.
  •  Mammalian G protein-coupled receptors that direct cellular chemotaxis. Advances in Protein Chemistry 68:393-444.
  •  Side chains at the membrane-water interface modulate the signaling state of a transmembrane receptor. Biochemistry 43:1763-1770.
  •  Membrane-docking loops of the cPLA2 C2 domain: Detailed structural analysis of the protein-membrane interface via site-directed spin-labeling. Biochemistry 42:13227-13240.
  •  Mapping out regions on the surface of the aspartate receptor which are essential for kinase activation. Biochemistry 42:2952-2959.
  •  C2 domain of protein kinase C-alpha: Elucidation of the membrane docking surface by site-directed fluorescence and spin labeling. Biochemistry 42:1254-1265.
  •  Quantitative analysis of the aspartate receptor signaling complex reveals that the homogeneous two-state model is inadequate: Development of a heterogeneous two-state model. J. Mol. Biol. 326:1597-1614.
  •  C2 domains of protein kinase C isoforms alpha, beta and gamma: Activation parameters and calcium stoichiometries of the membrane-bound state. Biochemistry 41:11411-11424.
  •  Membrane orientation and position of the cPLA2 C2 domain by site-directed spin labeling. Biochemistry 41:6282 -6292.
  •  Cooperativity between bacterial chemotaxis receptors. Proc. Natl. Acad. Sci. USA 99:6530-6532.
  •  Enzymology. A moving story. Science 295:1480-1481.
  •  Cation charge and size selectivity of the C2 domain of cytosolic phospholipase A(2). Biochemistry 41:1109-1122.
  • Use of fluorescence resonance energy transfer to monitor Ca2+-triggered membrane docking of C2 domains. Methods in Molecular Biology, Volume on Calcium-Binding Proteins Protocols. 172:295-303.
  •  Transmembrane signaling in bacterial chemoreceptors. Trends in Biochemical Sciences 26: 257-265.
  •  C2 domains from different Ca2+ signaling pathways display functional and mechanistic diversity. Biochemistry 40: 3089-3100.
  •  Evidence that both ligand binding and covalent adaptation drive a two-state equilibrium in the aspartate receptor signaling complex. Journal General Physiology 118:693-710.
  •  Purification of proteins using polyhistidine affinity tags. Methods in Enzymology 326:245-254.
  •  Structure of a conserved receptor domain that regulates kinase activity: the cytoplasmic domain of bacterial taxis receptors. Curr. Opin. Struct. Biol. 10:462-469.
  •  Attractant regulation of the aspartate receptor-kinase complex: limited cooperative interactions between receptors and effects of the receptor modification state. Biochemistry 39:9486-9493.
  •  The aspartate receptor cytoplasmic domain: In situ chemical analysis of structure, mechanism and dynamics. Structure 7: 829-840.
  •  Signaling domain of the aspartate receptor is a helical hairpin with a localized kinase docking surface: Cysteine and disulfide scanning studies. Biochemistry 38 :9317-9327.
  •  Identification of a site critical for kinase regulation on the central processing unit (CPU) helix of the aspartate receptor. Biochemistry 38: 329-36.
  • Location of the membrane-docking face on the Ca2+-activated C2 domain of cytosolic phospholipase A2. Biochemistry 37: 17642-50 (Accelerated Publication).
  •  The kinetic cycle of cardiac troponin C: Calcium binding and dissociation at site II trigger slow conformational rearrangements. Protein Science 7: 2451-9.
  •  Detection of a conserved a-helix in the kinase docking region of the aspartate receptor by cysteine and disulfide scanning. J. Biol. Chem. 273: 25006-25014.
  •  Cysteine and disulfide scanning reveals two amphiphillic helices in the linker region of the aspartate chemoreceptor. Biochemistry 37: 10746-10756.
  • Independent folding and ligand specificity of the C2 domain of cPLA2. J. Biol. Chem. 273: 1365-1372.
  •  Cysteine and disulfide scanning reveals a regulatory a-helix in the cytoplasmic domain of the aspartate receptor. J. Biol. Chem. 272: 32878-32888.
  •  The calcium signaling cycle of a membrane-docking C2 domain. Biochemistry 36: 12011-12018 (Accelerated Publication).
  •  Bacterial chemotaxis: A molecular view of signal transduction by receptors, kinases and signaling enzymes. Ann. Rev. Cell. Devel. Biol. 13: 457-512.
  •  Optimizing the metal binding parameters of an EF-hand-like calcium chelation loop: Coordinating side chains play a more important tuning role than chelation loop flexibility. Biochemistry 36: 9917-9926.
  •  Molecular tuning of an EF-hand-like calcium binding loop: Contributions of loop position 3. J. Gen. Physiol. 110: 173-184.
  •  Intramolecular tuning of calmodulin by target peptides and proteins: Differential effects on calcium binding and implications for kinase regulation. Prot. Science 6: 794-807.
  •  The C2 domain calcium binding motif: Structural and functional diversity. Protein Sci. 5: 2375-2390.
  •  Molecular mechanism of transmembrane signaling by the aspartate receptor: A model. PNAS 93: 2545-2550.
  •  Use of 19F NMR to probe protein structure and conformational changes. Ann. Rev. Biophys. Biomol. Struct. 25: 163-195.
  •  Effects of protein stabilizing agents on thermal backbone motions: A disulfide trapping study. Biochemistry 35: 10595-10600. (Accelerated Publication).
  •  Kinetic tuning of the EF-hand calcium binding motif: The gateway residue independently adjusts (i) barrier height and (ii) equilibrium. Biochemistry 35: 1753-1760.
  •  Tuning the equilibrium ion affinity and selectivity of the EF-hand calcium binding motif: Substitutions at the gateway position. Biochemistry 35: 6697-6705.
  •  Lock on/off disulfides identify the transmembrane signaling helix of the aspartate receptor. J. Biol. Chem. 270: 24043-24053.
  •  Transmembrane signaling by the aspartate receptor: Engineered disulfides reveal static regions of the subunit interface. Biochemistry 34: 9722-9733.
  •  Thermal hinge-twisting motions of protein domains in the D-galactose chemosensory receptor: detection by disulfide trapping. Biochemistry 34: 3048-3055.
  •  BLAST 1995: International conference on bacterial locomotion and signal transduction. Molecular Microbiology 16: 1037-1050.
  •  Molecular tuning of ion binding to calcium signaling proteins. Quart. Rev. Biophys. 27: 219-290.
  •  Attractant- and disulfide-induced conformational changes in the ligand binding domain of the chemotaxis aspartate receptor: A 19F NMR study. Biochemistry 33: 6100-6109.
  •  Novel ion specificity of a carboxylate cluster magnesium binding site in CheY: Strong charge selectivity and weak size selectivity. Biochemistry 32: 3363-3367.
  •  Activation of the phosphosignaling protein CheY. I. Analysis of the phosphorylated conformation by 19F NMR and protein engineering. J. Biol.. Chem. 268: 13081-13088.
  • Activation of the phosphosignaling protein CheY. II. Analysis of activated mutants by 19F NMR and protein engineering. R.B. J. Biol. Chem. 268: 13089-13096.
  •  Kinetic control of calcium signaling: Tuning the ion dissociation rates of EF-hand calcium binding sites. PNAS 90: 6493-6497.
 Thermal motions of surface alpha-helices in the D-galactose chemosensory receptor: Detection by disulfide trapping. J. Mol. Biol. 226: 1219-1235.
 Open conformation of a substrate binding cleft: 19F NMR studies of cleft angle in the D-galactose chemoreceptor. Biochemistry 30: 6484-6490.
 Structure of a bacterial sensory receptor. A site-directed sulfhydryl study. J. Biol. Chem. 263: 14850-14858.
 Global flexibility in a sensory receptor: A site-directed disulfide bond study. Science 237: 1596-1600.
  •  Inhibitors of band 3. I. Transport site inhibitors: A 35Cl NMR study. Biochemistry 25: 7888-7894.
  • Inhibitors of band 3. II. Translocation inhibitors: A 35Cl NMR study. J.J. Falke and S.I. Chan. Biochem. 25: 7895-7898.
  •  Inhibitors of band 3. III. Channel blockers: A 35Cl NMR study. J.J. Falke and S.I. Chan. Biochem 25: 7899-7906.