Disease relevance of PDCL

• In addition, we elucidated the mutational fingerprints of Phlp by analyzing Apc mutations in rat colon cancers induced by this carcinogen [1].

High impact information on PDCL

• Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly [2].
• Phosphorylation of PhLP at one or more of three consecutive serines (Ser-18, Ser-19, and Ser-20) is necessary for Gbetagamma dimer formation and is believed to be mediated by the protein kinase CK2 [3].
• Subsequent interaction of Gbetagamma with membranes releases PhLP for another round of assembly [3].
• Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2 [4].
• However, in the continued presence of norepinephrine, PDC or PDCL relieved calcium channel inhibition compared with control neurons [5].

Biological context of PDCL

• In this study, we identify new isoforms of the retinal phosducin and investigate the expression of the phosducin family, showing that an isoform, PhLP1, has sequence homology with Phd and Gbeta gamma binding capability, whereas two isoforms (phosducin-like orphan proteins, PhLOPs) share sequence homology with Phd but fail to bind Gbeta gamma [6].
• Regulation of exocytosis in chromaffin cells by phosducin-like protein, a protein interacting with G protein betagamma subunits [7].

Anatomical context of PDCL

• A proposed function of PDC and phosducin-like protein (PDCL) is the sequestration of "free" Gbetagamma from the plasma membrane, thereby terminating signaling by Gbetagamma [5].
• The functional impact of heterologously expressed PDC and PDCL on N-type calcium channel (CaV2.2) modulation was examined in sympathetic neurons, isolated from rat superior cervical ganglia, using whole-cell voltage clamp [5].
• Phosducin and phosducin-like proteins were found to bind and sequester the betagamma-subunits of G-proteins with implications for regulation of G-protein-mediated signaling pathways in various eukaryotic cells [8].
• In this report, we show that PhLP is phosphorylated in serum-stimulated Chinese hamster ovary (CHO) cells [9].
• T cell recognition of Phlp V was exclusively HLA-DR restricted [10].

Associations of PDCL with chemical compounds

• Indeed, we show here that histidine-tagged phosducin-like protein (His-PhLP) binds with high selectivity to both Ni2+-treated surface DNA and DNA-templated nickel metal to create linear protein assemblies on surfaces [11].
• Phosducin-like protein levels were measured in brain cortices of rats chronically treated with one of five classes of antidepressants: imipramine, venlafaxine, maprotiline, citalopram, and moclobemide [12].

Other interactions of PDCL

• Phosducin and phosducin-like protein attenuate G-protein-coupled receptor-mediated inhibition of voltage-gated calcium channels in rat sympathetic neurons [5].
• Analysis with antibodies raised against rat phosducin or human phosducin-like proteins, identified one major protein of a molecular weight of 28 kDa, and two protein bands of 40 kDa and 93 kDa [8].

References