Disease relevance of Pcsk4

• They also expressed tetanus toxin receptors, PC4, M1 and Thy-1 antigens [1].
• PC4 and PC13 (20 mg kg-1, i.p.) partly reversed hypothermia induced by low dose apomorphine (5 mg kg-1, s.c.) but were less effective for higher doses of apomorphine (16 mg kg-1, s.c.). At 200 mg kg-1, intraperitoneal PC13 enhanced the toxic effects of yohimbine (30 mg kg-1, s.c.), while PC4 was inactive [2].

Psychiatry related information on Pcsk4

• Only at intraperitoneal doses of 100 mg kg-1 did PC4 or PC13 significantly decrease locomotor activity [2].

High impact information on Pcsk4

• In vitro, the fertilizing ability of Pcsk4 null spermatozoa was also found to be significantly reduced [3].
• In an effort to elucidate this function, we have disrupted its locus (Pcsk4) by homologous recombination in embryonic stem cells and have produced mice carrying the mutation [3].
• Impaired fertility in mice deficient for the testicular germ-cell protease PC4 [3].
• PC4 is a member of the proprotein convertase family of serine proteases implicated in the processing of a variety of polypeptides including prohormones, proneuropeptides, and cell surface proteins [3].
• These results suggest that PC4 in the male may be important for achieving fertilization and for supporting early embryonic development in mice [3].

Biological context of Pcsk4

• These data suggest that PC4 represents a prime candidate for a precursor-processing endoprotease in the testicular germ cells and that its gene expression is regulated during spermatogenesis [4].
• The multiple forms of PC4 mRNA can all be explained by alternate splicing of primary transcripts of a single gene [5].
• The genes for three subtilisin/kexin-like proprotein convertases, PC4, PC5, and PACE4, were mapped in the mouse by RFLP analysis of a DNA panel from a (C57BL/6JEi x SPRET/Ei)F1 x SPRET/Ei backcross [6].
• These observations suggest that, within testis, PC4 is involved in processing of peptide precursors such as proenkephalin and may play a role in regulation of sperm maturation, while furin may serve as a more general processing endoprotease [7].
• Recent studies using PC4-transgenic mice revealed that male PC4-null mice exhibited severely impaired fertility, although spermatogenesis appeared to be normal [8].

Anatomical context of Pcsk4

• Northern blot analysis indicated that the PC4 mRNA was detectable only in the testes after the 20th day of postnatal development [4].
• Furin transcript was detected in both germ and somatic cells, while PC4 transcript was found only in round spermatids [7].
• In rodents, PC4 transcripts have been detected in spermatocytes and round spermatids exclusively, suggesting a reproductive function for this enzyme [3].
• However, whether PC4 is the sole endoprotease for the PACAP precursor in the gonads remains unknown [8].
• In the adult retina, only PC4 antigen is detectably expressed and is localized in the inner segments of photoreceptor cells [9].

Associations of Pcsk4 with chemical compounds

• Proprotein convertase 4 (PC4) is a mammalian secretory serine endoproteinase similar to the yeast KEX2 gene product and specifically expressed in testicular germs cells [5].
• The study concludes that the most probable sequence motif for recognition by PC4 is KXKXXR or KXXR, where X is any amino acid other than cysteine and that it prefers proline at P3, P5 and/or P2' positions [10].
• The potential antidepressant effects of two pyridazine derivatives, 5-benzyl 6-methyl 2-[4-(3-trifluoro-methyl phenyl) piperazin-1-yl] methylpyridazin-3-one (PC4) and 5-benzyl 6-methyl 2-[4-(3-chlorophenyl) piperazin-1-yl] methylpyridazin-3-one (PC13), were evaluated using classical psychopharmacological tests in mice [2].

Other interactions of Pcsk4

• PC4 is expressed only in the testis and ovary, where neither PC1 nor PC2 is expressed [8].
• PC4 antigen is normally detectable in the inner segments of photoreceptor cells, even when these have started to degenerate in the case of Purkinje cell degeneration [9].

Analytical, diagnostic and therapeutic context of Pcsk4

• Localization of Kex2-like processing endoproteases, furin and PC4, within mouse testis by in situ hybridization [7].
• This suggests that these fluorogenic peptides are useful for specific bioassay of PC4 activity [10].

References