Dual specificity kinase-enzyme

Most protein kinases can phosphorylate on Serine or Threonine, and a distinct group (TKs) phosphorylates on tyrosine. Dual-specificty kinases are those than overall belong to Ser/Thr kinase groups, but can also phosphorylate on tyrosine. Several DSKs are well known, though many others may have tyrosine kinase activity at a low level or under specific circumstances. Here is a summary of the reported dual-specificity kinase classes.

Dual Specificity Kinase DYRK3 Couples Stress Granule Condensation/Dissolution
to mTORC1 Signaling.

MEK kinases phosphorylate the activation loop of MAPK kinases, on both the T and Y of the TxY motif. Both phosphorylations are required for full activation of the MAPK. This motif is found in MAPKs throughout the eukaryotes, though some classes of MAPK lack the Y and are not activated by MEK kinases.

Dyrk family kinases autophosphorylate on tyrosine, but transphosphorylate only on Ser/Thr (hence the name: "Dual specificity Tyrosine Regulated Kinase"). The autophosphorylation occurs while still attached to the ribosome, and is an intramolecular reaction [2]. Autophosphorylation occurs on a Y (YxY in DYRK1) in the activation loop which is almost absolutely conserved across all DYRK subfamilies. However, human Dyrk1A is active without this tyrosine phosphorylation, as shown in vitro in phosphatase-treated enzyme, or in mutants in which the substrate Ys are removed.

The CLK family is related to DYRK, and members have been found to autophosphorylate and transphosphorylate on tyrosine in expression cloning in mammals, and in bacterial expression systems. However, in vivo substrates and physiological relevance of tyrosine phosphorylation is unclear. An activation loop tyrosine was seen to be phosphorylated in human CLK1, but this is only partially conserved.

The Casein kinase 2 (CK2) is a serine/threonine-selective protein kinase that is a tetramer of two alpha subunits and two beta subunits. The alpha subunits have the catalytic kinase domain. Casein kinase 2 has been implicated in cell cycle control, DNA repair, regulation of the circadian rhythm and other cellular processes.

MEK Family Kinase

DSTYK Family Kinase