Disease relevance of Pkia

• A comparison of inhibitory potencies of PKIalpha and PKIgamma expressed in Escherichia coli revealed that PKIgamma was a potent competitive inhibitor of Calpha phosphotransferase activity in vitro (Ki = 0.44 nM) but is 6-fold less potent than PKIalpha (Ki = 0.073 nM) [1].

High impact information on Pkia

• The studies demonstrate that the PKI alpha isoform is abundant in many regions of the adult mouse brain but particularly in cerebellum, hypothalamus, hippocampus, and cortex [2].
• The PKIbeta mutants were crossed with our previously derived PKIalpha mutants to obtain double-knockout mice [3].
• Specific testicular cellular localization and hormonal regulation of the PKIalpha and PKIbeta isoforms of the inhibitor protein of the cAMP-dependent protein kinase [4].
• The FSH-regulated expression of PKIalpha in the Sertoli cell likely occurs via the normal route of second messenger signal transduction [4].
• We now report that in the testis, there is a unique cellular distribution of protein kinase inhibitor forms, with PKIbeta being essentially (if not exclusively) a germ cell protein and PKIalpha being expressed primarily in Sertoli cells [4].

Biological context of Pkia

• The PKIgamma cDNA sequence determined here predicted an open reading frame of 75 amino acids, showing 35% identity to PKIalpha and 30% identity to PKIbeta1 [1].
• Residues important for the high affinity of PKIalpha and PKIbeta1 as well as nuclear export of the catalytic (C) subunit of cAMP-dependent protein kinase were found to be conserved in PKIgamma [1].

Anatomical context of Pkia

• In summary, endothelial cells from three different vascular beds express PKI alpha and PKI gamma, which may be physiologically important in endothelial barrier function [5].

Associations of Pkia with chemical compounds

• Site-directed mutagenesis of specific residues within this region implicates the presence of a tyrosine at position 7 in PKI alpha as a major contributor to its enhanced inhibitory potency [6].
• Specifically, three full-length, single-site PKI alpha mutants (V3C, S28C, and S59C) were prepared, and fluorescein iodoacetamide (FI) was selectively conjugated to the side chains of each substituted cysteine [7].

References