High impact information on cdk5

• Using explants of animal pole tissue from blastula embryos, which will differentiate into mesoderm in response to activin, we show that blocking cdk5 kinase activity down-regulates the expression of the muscle marker muscle actin in response to activin, whereas the pan-mesodermal marker Xbra is unaffected [1].
• Xp35.1 is expressed in both proliferating and differentiated neural and mesodermal cells and is particularly high in developing somites where cdk5 is also expressed [1].
• Thus, we have demonstrated a novel role for cdk5 in regulating myogenesis in the early embryo [1].
• This early expression of Xenopus cdk5 mRNA implies a role for cdk5 during embryogenesis that is separate from its role as an axonal cytoskeletal protein kinase [2].
• The high degree of sequence homology and shared neuronal expression suggests that the role of cdk5 in neurons is highly conserved between mammals and amphibians [2].

Biological context of cdk5

• These observations provide the foundation for exploiting X. laevis embryos to study the role of cdk5 both in the early stages of axonal differentiation and also in early embryogenesis [2].
• As a first step in studying the role of cdk5 and its effects on neurofilaments during Xenopus neural development, four cDNA clones were isolated by screening a frog brain cDNA library at lowered stringency with a cDNA probe to rat cdk5 [2].
• In spite of similar enzymatic properties of cdk5/p26 and p34cdc2/cyclin B kinase, cdk5/p26 did not display M-phase promoting activity when assayed with a cell-free system of Xenopus egg extract [3].
• Dephosphorylated forms of NF-H and NF-M became reactive to antibodies recognizing in vivo phosphorylation sites (SMI31, 34, and 36, JJ31 and 51) by phosphorylation with cdk5/p26. cdk5/p26 showed similar enzymatic properties to p34cdc2/cyclin B kinase; the substrate specificity and inhibition by a p34cdc2 kinase specific inhibitor, butyrolactone I [3].

Anatomical context of cdk5

• In contrast to the association of the active kinase with microtubules, each of uncomplexed cdk5 and the 35 kDa regulatory subunit was differently distributed in the supernatant fraction and the pellet, respectively, by ultracentrifugation of the brain extract [3].

Associations of cdk5 with chemical compounds

• An essentially similar sensitivity to this olomoucine family of compounds was observed for the brain-specific cdk5/p35 kinase [4].

Other interactions of cdk5

• However, p34cdc2/cyclin B kinase was distinguished from cdk5/p26 by its binding to p13suc1 protein and by its reactivity to anti-p34cdc2 antibodies [3].

Analytical, diagnostic and therapeutic context of cdk5

• In situ hybridization demonstrated that the Xenopus cdk5 transcript, like that of mammals, was expressed in differentiated post-mitotic neurons [2].
• Northern blot analysis indicated that during Xenopus development, cdk5 mRNA was first expressed between the midblastula transition and gastrulation, which both occur long before neuronal differentiation [2].

References