Protein-tyrosine Kinase and GTPase Signals Cooperate to Phosphorylate and Activate Wiskott-Aldrich Syndrome Protein (WASP)/Neuronal WASP

Abstract

Protein-tyrosine kinases and RhoCells respond to the environment through the expression of transmembrane receptors that sense extracellular stimuli and activate an elaborate network of intracellular signaling molecules. Given the large number of different signaling molecules and the complex relationships between them, a major challenge is to understand how specific signals generate unique responses. The architecture of signaling networks plays an important role in achieving signaling specificity (1). The logical AND gate is a motif frequently found in such architectures. In a simple form, an AND gate is a molecule that requires two signaling inputs in order to generate an output (i.e. a molecule that responds in highly cooperative fashion to two binding partners). Although there are many examples of signaling molecules that are thought to behave in this fashion, quantitative input-output relationships have been measured in relatively few cases.

Binding and Function of Phosphotyrosines of the Ephrin A2 (EphA2) Receptor Using Synthetic Sterile α Motif (SAM) Domains

“…Thus, protein conformational features can override the binding affinity that unstructured Tyr(P)-containing polypeptides may have for SH2 proteins (43). This is in accordance with observations on other systems (45,46) and emphasizes the need for caution in the interpretation of data obtained using peptide libraries/protein fragments in the elucidation of cell signaling mechanisms.…”

Small molecule targeting Cdc42–intersectin interaction disrupts Golgi organization and suppresses cell motility

“…Results shown are averaged from three independent experiments (n = 3 per group) ± SE (**P < 0.01, *P < 0.05). (23,24). As shown in Fig.…”

Nucleation of an Allosteric Response via Ligand-induced Loop Folding

“…The gene was altered to encode a C-terminal (His) 6 tag, which does not interfere with the wild type protein's function (18). Cells were grown at 30°C in LB media and protein expression was induced by addition of IPTG at O.D.…”

“…Consequently, allosteric control operates in a broad range of macromolecules including oligomeric metabolic enzymes (aspartate transcarbamylase)(3) chaperonin machines (GroEL)(4), transcription regulatory proteins (lactose repressor)(5), multi-domain signal transduction proteins (N-WASP) (6), and small molecule-activated riboswitches (Adenine riboswitch) (7). Understanding allostery requires elucidation of the ApoBirA, the unliganded form of BirA, is monomeric, as evidenced by its crystal structure and gel filtration and sedimentation equilibrium studies (14).…”