Abstract
The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival. Protein kinase A (PKA), whose activation is triggered by cyclic adenosine monophosphate (cAMP), is widely distributed in various systems and tissues throughout the body and highly related to pathogenesis and progression of various kinds of diseases. The inhibition of PKA activation is essential for the study of PKA functions. Protein kinase inhibitor peptide (PKI) is a potent, heat-stable, and specific PKA inhibitor. It has been demonstrated that PKI can block PKA-mediated phosphorylase activation. Since then, researchers have a lot of knowledge about PKI. PKI is considered to be the most effective and specific method to inhibit PKA and is widely used in related research. In this review, we will first introduce the knowledge on the activation of PKA and mechanisms related on the inhibitory effects of PKI on PKA. Then, we will compare PKI-mediated PKA inhibition vs. several popular methods of PKA inhibition.
Highlights
The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival (Manning et al, 2002)
The amino acid sequences in the inhibitory domain of PKI are similar to the regulatory subunit of Protein kinase A (PKA) that allow them to bind to the PKA catalytic subunit and inhibit its activity (Dalton and Dewey, 2006)
It should be noted that in this regulatory process, two domains of PKI with unique functions are involved, namely the inhibitory domain near the NH2-terminus and the nuclear export signal (NES) domain located between the NH2-terminus and the COOH-terminus, where the former allows for the realization of the inhibition of the cAMPdependent protein kinase inhibition and the latter mediates the nuclear export of the catalytic subunits of the cAMPdependent protein kinase (Henderson and Eleftheriou, 2000; Dalton and Dewey, 2006)
Summary
The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival (Manning et al, 2002). The amino acid sequences in the inhibitory domain of PKI are similar to the regulatory subunit of PKA that allow them to bind to the PKA catalytic subunit and inhibit its activity (Dalton and Dewey, 2006). The free catalytic subunits of PKA are able to reassociate with the regulatory subunits to form the cAMP-dependent protein kinase holoenzyme and restore cAMP regulation to the cell (Dalton and Dewey, 2006) Through this process, PKI can function to regulate the amount of free PKA C in the nucleus. It should be noted that in this regulatory process, two domains of PKI with unique functions are involved, namely the inhibitory domain near the NH2-terminus and the NES domain located between the NH2-terminus and the COOH-terminus, where the former allows for the realization of the inhibition of the cAMPdependent protein kinase inhibition and the latter mediates the nuclear export of the catalytic subunits of the cAMPdependent protein kinase (Henderson and Eleftheriou, 2000; Dalton and Dewey, 2006)
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