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PKI(5-24) TFA 是一种强效、竞争性、合成的 PKA (cAMP 依赖性蛋白激酶) 抑制剂，Ki 为 2.3 nM。PKI(5-24) TFA 对应于天然存在的热稳定蛋白激酶抑制剂中的 5-24 残基。

PKI(5-24) TFA is a potent, competitive, and synthetic peptide inhibitor of PKA (cAMP-dependent protein kinase), with a Ki of 2.3 nM. PKI(5-24) TFA corresponds to residues 5-24 in the naturally occurring heat-stable protein kinase inhibitor.

PKI (5-24) acetate是PKA（cAMP依赖性蛋白激酶）的竞争性、不可逆的肽抑制剂（Ki=2.3nM）。

PKI (5-24) acetate is a competitive, non-reversible peptide inhibitor of PKA (cAMP-dependent protein kinase) (Ki = 2.3 nM).

20个残基的肽代表骨骼肌中cAMP依赖性蛋白激酶抑制剂蛋白的活性位点，以高亲和力与cAMP依赖性蛋白激酶结合并竞争性抑制酶活性。

20-residue peptide that represents the active site of the cAMP-dependent protein kinase inhibitor protein in skeletal muscle, binds to the cAMP-dependent protein kinase with high affinity and competitively inhibits enzyme activity.

环腺苷酸依赖蛋白激酶抑制剂 α(5-24)（人、小鼠、兔、大鼠）是一种保守抑制基序，设计用于结合蛋白激酶 A 的催化裂隙。序列的疏水与碱性残基实现选择性识别。其物种通用性支持比较生化研究。应用包括动力学分析、构象图谱与抑制剂设计。

"cAMP-Dependent Protein Kinase Inhibitor-α (5-24) (human, mouse, rabbit, rat) is a conserved inhibitory motif designed to engage the catalytic cleft of PKA. The sequences hydrophobic and basic residues enable selective recognition. Its species versatility supports comparative biochemical studies. Applications include kinetic analysis, conformational mapping, and inhibitor design."

Definition
Protein kinases are transferase that catalyze the phosphorylation of proteins by covalently attaching phosphate groups to them, using ATP as a phosphate donor. Reversible protein phosphorylation-dephosphorylation has a principal role in the regulation of essentially all cellular functions. Kinase/phosphatase substrates can be found grouped according to their kinase families. A single substrate can have a many number of modifications.

Discovery
Phoebus AL at the Rockefeller Institute identified phosphate in the protein Vitellin (phosvitin) in 1906 1 and by 1933 Fritz Lipmann had detected phosphoserine in Casein 2. In 1954 Eugene P. Kennedy described the first ‘enzymatic phosphorylation of proteins’ in a variety of normal and malignant tissues, he showed that the phosphorus of the phosphoprotein fraction undergoes a high rate of turnover, as measured by incorporation of 32P 3 .

Structural Characteristics
There are thousands of different kinds of proteins in any particular cell that are substrate for different kinases and phosphatases. Phosphorylation of any site on a given protein can change the structure, function or localization of that protein. Within a protein, phosphorylation can occur on several amino acids. Phosphorylation on serine is the most common, followed by threonine. Tyrosine phosphorylation is relatively rare. However, since tyrosine phosphorylated proteins are relatively easy to purify using antibodies, tyrosine phosphorylation sites are relatively well understood. Histidine and aspartate phosphorylation occurs in prokaryotes as part of two-component signaling and in some cases in eukaryotes in some signal transduction pathways 4. Phosphorylation of seryl or threonyl (and occasionally tyrosyl) residues triggers small conformational changes in these proteins that alter their biological properties.

Mode of Action
Phosphatase removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group. Protein kinases are the effectors of phosphorylation and catalyse the transfer of a y-phosphate from ATP to specific amino acids on proteins. The addition of a phosphate (PO4) molecule to a polar R group of an amino acid residue can turn a hydrophobic portion of a protein into a polar and extremely hydrophilic portion of molecule. In this way it can introduce a conformational change in the structure of the protein via interaction with other hydrophobic and hydrophilic residues in the protein. Several protein kinases are important in cellular control (e.g. glycogen synthase kinase-3, acetyl CoA carboxylase kinase, tyrosine hydroxylase kinase and casein kinase-2), which are themselves controlled by allosteric effectors, phosphorylation, insulin and other growth factors, or by regulators. Protein phosphatase catalytic units are responsible for dephosphorylating many regulated proteins in the cytoplasm that are phosphorylated on serine and threonine residues. Some protein phosphatases are controlled by second messengers. PP-1(Protein phosphatase-1) is regulated by cyclic AMP in several ways that vary with the form of the enzyme and the tissue. It is inhibited by cyclic AMP through the phosphorylation of inhibitor-1 and its isoforms  through the phosphorylation of targeting proteins such as the glycogen-binding subunit, and through allosteric inhibition by phosphorylase a. PP-2B (Protein phosphatase-2B)  is activated by Ca2+ through the interaction of this second messenger with an integral Ca2+ -binding subunit, as well as calmodulin itself. Protein phosphorylation-dephosphorylation is the basis of a network of interlocking systems that allow hormones and other extracellular signals, acting through just a few second messengers, to coordinate biochemical functions 5.

Functions
Reversible phosphorylation of proteins is an important regulatory mechanism that occurs in living cells 6. Reversible phosphorylation results in a change in conformation the structure in many enzymes and receptors, causing them to become activated or deactivated.
Regulatory roles, the p53 protein is heavily regulated through phosphorylation sites, it has 18 different phosphorylation sites. Activation and phosphorylation of p53 can lead to cell cycle arrest, which can be reversed under some circumstances, or apoptotic cell death 7. In energy-requiring reactions, phosphorylation of Na+/K+-ATPase during the transport of sodium (Na+) and potassium(K+) ions across the cell membrane in osmoregulation to maintain homeostasis.
Enzyme regulation, phosphorylation of the enzyme GSK-3 by AKT (Protein kinase B) is a important regulation in insulin signaling pathway.
Protein-protein interaction, phosphorylation of the cytosolic components of NADPH oxidase, a large membrane-bound, multi-protein enzyme plays an important role in the regulation of protein-protein interactions of the enzyme.
Protein degradation, phosphorylation of some proteins causes them to be degraded by the ATP-dependent ubiquitin/proteasome pathway. These proteins become substrates for particular E3 ubiquitin ligases only when they are phosphorylated 8.

References

1.     Levene PA, Alsberg CL (1906). The cleavage products of vitellin. J. Biol. Chem., 2(1): 127-133.

2.     Lipmann FA, Levene PA (1932). Serinephosphoric acid obtained on hydrolysis of vitellinic acid. J. Biol. Chem., 98 (1):109-114.

3.     Burnett G, Kennedy EP (1954). The enzymatic phosphorylation of proteins. J. Biol. Chem., 211(2):969–980.

4.     Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD (2005). A simplified laminin nomenclature. Matrix Biol., 24(5):326-332.

5.     Cohen P (1988). Protein Phosphorylation and Hormone Action. Proceedings of the Royal Society of London. Biological Sciences, 234(1275):115-144.

6.     Barford D, Das AK, Egloff MP (1998). The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu Rev Biophys Biomol Struct., 27:133–164.

7.     Ashcroft M, Kubbutat MH, Vousden KH (1999). Regulation of p53 function and stability by phosphorylation. Mol. Cell. Biol., 19(3):1751–1758.

8.     Babior BM (1999). NADPH oxidase: an update. Blood, 93(5):1464–1476.

Cheng HC, et al. A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase. J Biol Chem. 1986;261(3):989-992. : https://pubmed.ncbi.nlm.nih.gov/3511044/
Ruth P, et al F. A cGMP kinase mutant with increased sensitivity to the protein kinase inhibitor peptide PKI(5-24). Biol Chem. 1996;377(7-8):513-520. : https://pubmed.ncbi.nlm.nih.gov/8922286/