Interaction of Gbetagamma with RACK1 and other WD40 repeat proteins.
Heterotrimeric G-proteins, composed of Galpha and Gbetagamma subunits, transmit numerous and diverse extracellular stimuli via a large family of heptahelical cell-surface receptors to various intracellular effector molecules. The Gbetagamma subunit plays a central role in G-protein signaling. The Gbeta subunit belongs to a large family of WD40 repeat proteins, which adopt a circular beta-bladed propeller structure. This unique structural feature confers interactions of Gbetagamma with a variety of proteins to play diverse functions. Intriguingly, we recently found that Gbetagamma can interact with three other WD40 repeat proteins, receptor for activated C kinase 1 (RACK1), dynein intermediate chain-1A and a protein of unknown function. This raises the following questions: are interactions among WD40 proteins a common theme and does the formation of a WD40-WD40 repeat protein complex constitute a protein scaffold for integrating signals from different cellular processes. We are beginning to address these issues by studying the interaction between Gbetagamma and RACK1. Here we will describe the molecular mechanism underlying this interaction and the implications of the interaction on the signal transduction of G-protein and RACK1.
Department of Pharmacology, Vanderbilt University Medical Center, Room 442, Robinson Research Building, Nashville, TN 37232, USA. Songhai.Chen@Vanderbilt.edu
Songhai
S
Chen
Bryan D
BD
Spiegelberg
Fang
F
Lin
Edward J
EJ
Dell
Heidi E
HE
Hamm
D000595:Amino Acid Sequence; D000818:Animals; D044385:GTP-Binding Protein alpha Subunits / Q000502:physiology; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism* / Q000502:physiology; D006321:Heart / Q000502:physiology; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology; D020449:Repetitive Sequences, Amino Acid; D015398:Signal Transduction
D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008840:Microfilament Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface