One of the most important methods in cellular communication is the addition or
removal of phosphate groups in proteins or lipids along the signal
... [Show More] transduction pathways in eukaryotic cells. Phosphorylation of proteins can control their enzymatic activity, their interaction with other proteins and molecules, their location in the cell, and their propensity for degradation by proteases. Dysregulation of many kinases has been linked to disease development, especially in cancer development.Kinases catalyze the transfer of g-phosphate groups from ATP to a hydroxyl group in proteins or lipids. The hydrolysis of ATP generates adenosine 50
-diphosphate(ADP) in this process as a by-product. Opposite to the phosphorylation, the removal of the phosphate group from phosphorylated proteins is catalyzed by phosphatases. The g-phosphate group in ATP can be transferred to either serine/threonine or tyrosine
residues in a substrate protein in the presence of protein kinases. Based on this,
the Enzyme Committee classifies protein kinases into two large families: Ser/Thr
kinases (EC2.7.11) if the phosphate group is transferred to serine or threonine residues and Tyr kinases (EC2.7.10) if the phosphate group is transferred to tyrosine residues.Protein genome-wide searches revealed that there are a total 518 putative
kinases genes in the human genome. Of these, 478 genes encode protein kinases,
and 40 genes encode atypical protein kinases that are proteins having biochemical
kinase activities but lacking sequence similarity to protein kinase domain. Fifty of
the 478 protein kinases lack at least one of the conserved catalytic residues (Lys30,
Asp125, and Asp143) and are likely to be catalytically inactive. Thus, only about 468
catalytically active protein kinases can phosphorylate cellular proteins. Based on the classification method originally developed by Steven K. Hanks (1988), human protein kinases can be classified into seven groups based on sequence similarity and catalytic
domains (AGC, CaMK, CK1, CMGC, STE, TK, and TKL). The AGC group includes
the PKA, PKC, and PKG families of kinases. The CaMK group comprises the kinases
that are regulated by calmodulin, which are important in the process of neural transmission.
The CK1 group comprises the casein kinase 1 family kinases. The CMGC
group contains the cyclin-dependent kinases (CDKs) and mitogen-activated protein
kinases (MAPKs). These kinases are key components of a number of signal [Show Less]