Rabbit Anti-Human DYRK4 (a.a. 104-400) Polyclonal antibody

In a neuronal overexpression screen focused on kinases and phosphatases, one 'hit" was the dual specificity tyrosine phosphorylation-regulated kinase (Dyrk4), which increased the number of dendritic branches in hippocampal neurons. Overexpression of various Dyrk family members in primary neurons significantly changed neuronal morphology. Dyrk1A decreased axon growth, Dyrk3 and Dyrk4 increased dendritic branching, and Dyrk2 decreased both axon and dendrite growth and branching. Kinase-deficient mutants revealed that most of these effects depend on kinase activity. Because doublecortin (DCX), a microtubule-binding protein, regulates cytoskeletal dynamics and neuronal morphogenesis, we investigated the possibility that DCX is a target of Dyrks. We found that overexpression of Dyrk2 and Dyrk3, but not Dyrk1A or Dyrk4, can change DCX phosphorylation status. Mutation of a consensus phosphorylation site for Dyrk kinases at Serine 306 (Ser306) in DCX indicated that this is one target site for Dyrk2 and Dyrk3. Overexpression of Dyrk2 restored altered DCX distribution in the growth cones of dendrites and axons, and partially reversed the morphological effects of DCX overexpression; some of these effects were abrogated by mutation of Ser306 to alanine. These studies implicate Dyrks in the regulation of cytoskeletal organization and process outgrowth in neurons, and suggest that DCX is one relevant Dyrk target. (C) 2012 Wiley Periodicals, Inc

The human teratocarcinoma cell line NTERA-2 cl.D1 (NT2 cells) can be induced with retinoic acid and cell aggregation to yield postmitotic neurones. This seems to model the in vivo situation, as high concentrations of retinoic acid, retinoic acid binding proteins, and receptors have been detected in the embryonic CNS and the developing spinal cord suggesting a role for retinoic acid in neurogenesis. Suppression subtractive hybridization was used to detect genes up-regulated by this paradigm of neuronal differentiation. Microfibril-associated glycoprotein 2 was found to be drastically up-regulated and has not been implicated in neuronal differentiation before. Suppression subtractive hybridization also identified DYRK4, a homologue of the Drosophila gene minibrain. Minibrain mutations result in specific defects in the development of the fly central nervous system, In adult rats, DYRK4 is only expressed in testis, but our results suggest an additional role for DYRK4 in neuronal differentiation. We have shown that suppression subtractive hybridization in conjunction with an efficient screening procedure is a valuable tool to produce a repertoire of differentially expressed genes and propose a new physiological role for several identified genes and expressed sequence tags.