Disease relevance of PRP-2

• Two phages (PRP1 and PRP2) hybridizing to the rat probe under moderately stringent conditions contain related but not identical DNAs [1].
• In an attempt to establish a cell line in which it would be possible to regulate proline-rich protein gene transcription, rat parotid gland cells were fused with the rat hepatoma cell line, FTO-2B [2].
• Gland hypertrophy showed the same differential dosage kinetics, based on gland weight, between the two glands; however, hypertrophy could be accomplished at a lower dosage of isoprenaline than that used to induce proline-rich-protein biosynthesis [3].
• The effect of new heparin mimetics (synthetic oligosaccharides) was studied in vitro with regard to thrombin generation (TG) in rat platelet rich plasma (PRP) and whole blood (WB) and in vivo on stasis-induced venous thrombosis in the rat [4].
• We evaluated the acute expression of Nogo-A, the Nogo-66 receptor (NgR) and the novel small proline-rich repeat protein 1A (SPRR1A, previously undetected in brain), following experimental lateral fluid percussion (FP) brain injury in rats [5].

High impact information on PRP-2

• Identification of a ten-amino acid proline-rich SH3 binding site [6].
• RBPs contain three Src homology 3 domains that bind to proline-rich motifs in alpha(1) subunits and Rab3-interacting molecules (RIMs) [7].
• Homer EVH1 (Ena/VASP Homology 1) domains interact with proline-rich motifs in the cytoplasmic regions of group 1 metabotropic glutamate receptors (mGluRs), inositol-1,4,5-trisphosphate receptors (IP3Rs), and Shank proteins [8].
• Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors [9].
• This patch accounts for the specific requirement of amphiphysin for two arginines in the proline-rich binding motif to which it binds on dynamin [10].

Chemical compound and disease context of PRP-2

• This same regimen of beta-receptor agonists was unable to induce submandibular gland hypertrophy, PRP or glycoprotein biosynthesis in the same animals [11].
• Reperfusion of the rat hearts (at 30 min ischemia) was followed by partial recovery of PCr (44 +/- 3%) and Na+i (234 +/- 69%) and poorer recovery of the pressure-rate product (PRP, 9 +/- 4%) and end-diastolic pressure (EDP, 72 +/- 5 mmHg) compared to the pig hearts (PCr, 106 +/- 25%; Na+i, 82 +/- 17%; PRP, 24 +/- 3%; EDP, 4.6 +/- 2.5 mmHg) [12].
• These results may be related to the ability of the glutamine/proline-rich protein PQE-1 to protect C. elegans against polyglutamine toxicity [13].

Biological context of PRP-2

• The high degree of conservation of both nucleotide and amino acid sequence in the entire unit also indicates that the PRP gene(s) likely evolved by multiplication of a 300-base pair ancestral DNA sequence [14].
• This oligonucleotide was used as an efficient primer for the construction of a PRP-specific lambda gt10 cDNA library [14].
• The 4.4-kilodalton proline-rich polypeptides of the rat ventral prostate are the proteolytic products of a 637-kilodalton protein displaying highly repetitive sequences and encoded in a single exon [15].
• Deletion of the TBM affects transcriptional activity slightly, but it is adjacent to a proline-rich sequence which constitutes the major transactivation domain [16].
• Both proteins contain COOH-terminal proline-rich domains that can interact with a variety of Src homology 3 (SH3) domains [17].

Anatomical context of PRP-2

• Within 3 days the parotid glands were enlarged about 3-fold and a series of proline-rich proteins were increased about 12-fold [18].
• Finally, we found that deletion of the PR sequence from a constitutively activated MEK1 mutant rendered the protein nontransforming in Rat1 fibroblasts [19].
• Salivary gland cells, however, are difficult to maintain in a differentiated state in culture and can be induced to synthesize proline-rich protein mRNAs for only a few days [2].
• Regulation of proline-rich protein and alpha-amylase genes in parotid-hepatoma hybrid cells [2].
• These acid-soluble substances were obtained by extracting tissues with 10% trichloroacetic acid, as reported previously for isolating proline-rich proteins from rat submandibular glands (Mehansho, H., and Carlson, D.M. (1983) J [20].

Associations of PRP-2 with chemical compounds

• A single 12.5-kilobase androgen-regulated mRNA encoding multiple proline-rich polypeptides in the ventral prostate of the rat [14].
• Amino acid analyses, electrophoretic patterns, and cell-free translations of mRNAs all confirmed that the proline-rich proteins induced by feeding high-tannin sorghum were identical to those induced by isoproterenol treatment [18].
• This is unlike other proline-rich peptides complexed to WW domains, which bind in an extended conformation and lack molecular interactions with residues C-terminal to the tyrosine or the structurally equivalent residue in non-PY motif WW domain targets [21].
• Modulation of proline-rich protein biosynthesis in rat parotid glands by sorghums with high tannin levels [18].
• The hybrid cells exhibited induced proline-rich protein mRNA synthesis when incubated with either dibutyryl cyclic AMP or forskolin [2].

Physical interactions of PRP-2

• We have recently identified the ubiquitin-protein ligase Nedd4 as an interacting protein with ENaC and demonstrated that Nedd4 binds by its WW domains to the proline-rich PY motifs of ENaC [22].

Regulatory relationships of PRP-2

• Phosphospecific site tyrosine phosphorylation of p125FAK and proline-rich kinase 2 is differentially regulated by cholecystokinin receptor type A activation in pancreatic acini [23].

Other interactions of PRP-2

• We have used the proline-rich tail of synaptojanin to screen a rat brain library by the two-hybrid method to identify additional interacting partners of synaptojanin [17].
• Synamon has seven ankyrin repeats at the NH(2) terminus followed by one src homology 3 domain and one PSD-95/Dlg-A/ZO-1 domain, and several proline-rich regions at the carboxyl terminus [24].
• Previously, we solved the NMR structure of the central proline-rich P-domain of CRT comprising residues 189-288 [25].
• Agonist activation of endogenous angiotensin II (Ang II) AT(1) receptors expressed in hepatic C9 cells markedly stimulated inositol phosphate production, phosphorylation of the proline-rich tyrosine kinase PyK-2, and ERK activation [26].
• We found that, in astrocytes, thrombin can evoke phosphorylation of proline-rich tyrosine kinase (Pyk2) via PAR-1 [27].

Analytical, diagnostic and therapeutic context of PRP-2

• A 2-4-fold increase in proline-rich protein mRNAs was observed in rat parotid glands as soon as 4 h after treatment [28].
• Northern blot analysis of RNAs from parotid glands of normal and isoproterenol-treated rats, probed with a 32P-labeled proline-rich protein cDNA, confirmed that control animals were devoid of mRNAs encoding these proteins and that isoproterenol treatment dramatically induced expression of these genes [20].
• After perfusion of platelet-rich plasma (PRP) through the aortas of animals of the two strains, platelet aggregability, already lower in the IVA-SIV, was reduced to a higher extent compared to the CR [29].
• Elimination of isoproterenol-induced proline-rich protein biosynthesis in rat salivary glands after adult thyroidectomy [30].
• Western blot analysis with antibodies to submandibular gland mucin, glutamine/glutamic-acid-rich protein (GRP), and proline-rich proteins (PRP) were also utilized to compare the effects of autonomic drugs on these salivary proteins [31].

References