Cell Signaling Transduction Related Protein Kinase

Cell Signaling Transduction Related Protein Kinase Information

Cells can react to environmental changes by transduction of extracellular signals, to produce intracellular responses. Membrane-impermeable signal molecules are recognized by receptors, which are localized on the plasma membrane of the cell. Binding of a ligand can result in the stimulation of an intrinsic enzymatic activity of its receptor or the modulation of a transducing protein. The modulation of one or more intracellular transducing proteins can finally lead to the activation or inhibition of a so-called ‘effector protein’. In many instances, this also results in altered gene expression. Phosphorylation by protein kinases is one of the most common and important regulatory mechanisms in cell signaling transduction. There are many groups of protein kinases involved in cell signaling trasduction, including the AGC group……

The functions of protein kinase in cell signaling transduction

One of the most important function of protein kinase in cell signaling transduciton is Phosphorylation. Phosphorylation is an extremely important type of modification. When a molecule is phosphorylated, the γ-phosphate of ATP is transferred onto it by a kinase. Phosphorylation of a protein can either activate or inhibit it. The AP-1 (Fos/Jun) transcription factor cJun contains phosphorylation sites at its N-terminus and near the downstream DNA binding region. N-terminal phosphorylation (by MAPK family members) is involved in cJun activation, whereas phosphorylation near the DNA binding site (by GSK-3) silences cJun [70]. Phosphorylation of tyrosine residues can also create highly selective docking sites for SH2 or other PY binding domain containing proteins. The presence of protein phosphatases allows switching between active and inactive states of proteins and their complexes: they dephosphorylate their targets by removing phosphate modifications.

The AGC group of protein kinases in cell signaling transduction

The AGC group serine/threonine protein kinases tend to be basic amino acid-directed enzymes. Many of these kinases are activated upon the release of second messengers. The AGC group includes the cyclic nucleotide regulated protein kinase (PKA, PKG) family, the PKC family (see below), the ‘RAC’ (PKB/Akt) family, the GPCR kinase family and the ribosomal S6 protein kinase family.

The CaMK group of protein kinases in cell signaling transduction

The CaMK group serine/threonine protein kinases tend to be basic amino acid-directed as well. Regulation via second messenger pathways is also common for this group. The CaMK group includes the Ca2+/calmodulin-dependent kinase (CaMK) and SNF1/AMPK families.

The CMGC group of protein kinases in cell signaling transduction

The CMGC group serine/threonine kinases are not regulated by second messengers, but act further downstream protein kinase cascades. These kinases commonly exhibit regulatory phosphorylation sites in the activation segment. The CMGC group includes the CDK (cyclin-dependent kinase) family, the MAPK/ERK family, the GSK-3 family and the Clk (Cdc-like kinase) family.

The conventional protein tyrosine kinase group in cell signaling transduction

The group of the conventional protein tyrosine kinases (PTKs) differs from all the other groups in that the members exclusively phosphorylate tyrosine residues. PTKs are often involved in the transduction of growth and differentiation signals in metazoans. The most important sequence differences between the serine/threonine and conventional tyrosine kinases lie within the catalytic loop and the activation segment. A sequence according to the HRDLKxxN motif in the catalytic loop (subdomain VIb) indicates serine/threonine specificity; HRDLRAAN and HRDLAARN are the consensus sequences indicative of conventional non-receptor PTKs and RTKs, respectively. In the activation segment, there is a conserved threonine in serine/threonine kinases; in PTKs, the equivalent residue is a proline. This could create a more open site for the larger tyrosine substrate residue to be accommodated.

The group of ‘other’ protein kinases in cell signaling transduction

The protein kinases falling outside the four major groups are combined in the group of ‘other’ kinases, including the MEK/Ste7p family, the MEKK/Ste11p family, the PAK/Ste20p family, the Raf family, the activin/TGF-β receptor family, the flowering plant receptor kinase family, the casein kinase I family and the LIM kinases.

Cell Signaling Transduction Related Protein Kinase Reference

• Schenk P W, et al. Signal perception and transduction: the role of protein kinases[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1999, 1449(1): 1-24.

Cell Signaling Transduction