Disease relevance of Pdcl

• Here we report the expression of PhLP in Escherichia coli and its purification [1].
• Results of pertussis toxin sensitivity, GTPgammaS binding, and immunoprecipitation experiments suggest that PhLP inhibits phospholipase Cbeta activation by dual mechanisms: (i) steric blockage of Gbetagamma activation of PLCbeta and (ii) interference with Gbetagamma-dependent cycling of G(q)alpha by the receptor [2].

High impact information on Pdcl

• Unlike protein-folding substrates of CCT, which interact only in their nonnative conformations, PhLP binds in its native state [3].
• The IC50 value of PhLP in the latter assay was 89 nM, whereas phosducin caused half-maximal inhibition at 17 nM [1].
• And finally, PhLP antagonized the enhancement of rhodopsin phosphorylation by purified betagamma subunits [1].
• Phosducin-like protein: an ethanol-responsive potential modulator of guanine nucleotide-binding protein function [4].
• We identified from a rat brain cDNA library an isolate encoding the phosducin-like protein (PhLP), which has 41% identity and 65% amino acid homology to phosducin [4].

Biological context of Pdcl

• We have identified four forms of PhLP cDNA varying only in their 5' ends, probably due to alternative splicing [4].
• Induction of PhLP by ethanol could account for at least some of the widespread alterations in signal transduction and G-protein function that are known to occur with chronic exposure to ethanol [4].
• Gene expression of the phosducin-like protein in the retina [5].

Anatomical context of Pdcl

• Phosducin and phosducin-like protein regulate G protein signaling pathways by binding the betagamma subunit complex (Gbetagamma) and blocking Gbetagamma association with Galpha subunits, effector enzymes, or membranes [6].

Associations of Pdcl with chemical compounds

• Treatment of NG108-15 cells for 24 hr with concentrations of ethanol seen in actively drinking alcoholics (25-100 mM) causes up to a 3-fold increase in PhLP mRNA levels [4].
• This 5'-end variation generates two predicted forms of PhLP protein that differ by 79 aa at the NH2 terminus [4].
• Regulation of angiotensin II-induced G protein signaling by phosducin-like protein [2].
• Up to 3.6-fold overexpression of PhLP had no effect on Ang II-stimulated inositol trisphosphate (IP(3)) formation, whereas further increases caused an abrupt decrease in IP(3) production with half-maximal inhibition occurring at 6-fold PhLP overexpression [2].

Other interactions of Pdcl

• Role of the isoprenyl pocket of the G protein beta gamma subunit complex in the binding of phosducin and phosducin-like protein [7].

References