The nuclear lamina is an intermediate filament-type network underlying the inner nuclear membrane. Phosphorylation of lamin proteins is believed to cause lamina disassembly during meiotic and mitotic M phase, but the M phase-specific lamin kinase has not been identified. Here we show that the cdc2 kinase, a major element implicated in controlling the eukaryotic cell cycle, phosphorylates chicken B-type lamins in vitro on sites that are specifically phosphorylated during M phase in vivo. Concomitantly, cdc2 kinase is capable of inducing lamina depolymerization upon incubation with isolated nuclei. One of the target sites of cdc2 kinase is identified as a motif (SPTR) conserved in the N-terminal domain of all lamin proteins. These results lead us to propose that mitotic disassembly of the nuclear lamina results from direct phosphorylation of lamins by cdc2 kinase.

The nuclear lamina is a fibrillar protein meshwork underlying the inner nuclear membrane. Its major constituents, the lamins, are members of the intermediate filament protein family (eg, McKeon et al., 1966; Fisher et al., 1986; Aebi et al., 1986; Franke, 1987). Based on biochemical properties and structural criteria most vertebrate lamins can be classified as either A-or B-type lamins (Hiiger et al., 1988; Peter et al., 1989; Vorburger et al., 1989a; for reviews see Gerace and Burke, 1988; Nigg, 1989). B-type lamins remain associated with the nuclear membrane throughout the cell cycle, but A-type lamins are completely solubilized during mitosis (Gerace and Blobel, 1980; Stick et al., 1988). In birds and mammals, expression of at least two B-type lamins is characteristic of most somatic cells (Lehner et al., 1986; Vorburger et al., 1989a; Weber et al., 1990), whereas little or no A-type lamins are expressed in early embryos (Lehner et al., 1987; Stewart and Burke, 1987; Wolin et al., 1987; Ribber et al., 1989). During interphase (I phase), the nuclear lamina is believed to be important for nuclear envelope integrity and