PubMed: 8282104

Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5.
FEBS letters
Mandelkow E | Biernat J | Baumann K | Piwnica-Worms H | Mandelkow EM

Evidence fe3ef613d7

Fig. 5 shows that the 31 kDa kinase is included in the MAP fraction after three or more cycles of microtubule assembly (lanes l-6), and is also associated with PHFs (lane 7)

Evidence 4d4cc20c8b

In this regard, cdk5 is similar to PKA [30], MAP kinase, and GSK-3 [12,17,26], but distinct from PKC or CaMK which do not copurify with microtubules [34]

Evidence 4a787dbcb7

These fractions (7-9) contained several protein bands, including two with Mr = 25 and 31 kDa (Fig. 3D, lanes 3-5) and were capable of phosphorylating htau40, incorporating 3.2, 4.2 and 2.9 mol Pi per mol htau40, respectively, and inducing an A4, shift of htau40 in SDS-PAGE

Evidence 0d7e9a8420

We find that this kinase shows good activity towards tau only when complexed with another protein of Mr 25 kDa, presumably a regulatory subunit analogous to one of the cyclins

Evidence fa9b3faffc

In conclusion, this cdc2-like kinase activity towards tau occurs in brain tissue and has an Mr of 31 kDa. These features are suggestive of other cdc2-like kinases cloned recently from brain, termed nclk [ 141, PSSARLE [28], or cdk5 [42,49]. Indeed, the 31 kDa protein reacted with an antibody specific for cdk5. Thus, the kinase isolated here is very similar if not identical to cdk5.

Evidence 916eee1a3b

The reaction with the diagnostic antibodies (Fig. 4) is similar to the examples shown previously for cdk2 (Fig. 2), MAP kinase [8], or GSK-3 [26], indicating the phosphorylation of the SP motifs for which these antibodies are sensitive (serines 199, 202, 235, 396, 404; see Fig. 1)

Evidence 63dceea01b

Thus, we now know three kinases, cdk5, MAP kinase, and GSK-3, all of which are present in neurons, which are capable of transforming tau into the Alzheimer-like state, and therefore could account for the pathological phosphorylation of tau in Alzheimer brains

Evidence 70839e6f55

The Mr shifts up with time in several stages, very similar to our earlier observations with the brain kinase activity, MAP kinase and GSK3 (Fig. 2,)

Evidence 1ec0f901c3

The diagnostic antibodies AT8, TAU-1, SM131, SM134, and SM133 react to phosphorylation similarly as with MAPK and GSK-3, indicating that SP motifs before the repeat region (S199 and/or S202, S235) and after the repeats (S396, S404) become phosphorylated (Fig. 2,-2,); note that AT8, SMUl, and SM134 react with PHFs where the epitopes containing SP motifs are phosphorylated, while TAU-1 and SM133 react with normal tau where the epitopes are not phosphorylated


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