TI - Functional analysis of phosphorylation sites in human lamin A controlling lamin disassembly , nuclear transport and assembly . AB - We have constructed point mutations in human lamin A cDNA at conserved serine and threonine residues , some of which were shown to be phosphorylated in vitro by cdc2-kinase and protein kinase C and in vivo . Using a functional in vivo assay system , we identified three categories of mutant phenotypes . (i) Dominant negative phenotypes in mitosis result from mutation of Thr-19 and Ser-22 within the amino - terminal cdc2-kinase motif of lamin A . An increase of aberrant mitotic phenotypes in the double mutants Thr-19/Ser-392 and Ser-22/Ser-392 suggests that concomitant phosphorylation of the three residues regulates mitotic lamin A disassembly. ( ii ) Mutation of both Ser-403/Ser-404 within a PKC motif flanking the nuclear localization signal inhibits transport of mutant lamin A to the nucleus in 64% of the cells . It is proposed that phosphorylation of the motif in vivo positively regulates nuclear localization together with the nuclear localization sequence. ( iii ) The assembly of lamin A into the perinuclear lamina is disturbed by mutation of the carboxy - terminal Ser-525 , previously shown to be interphase-specifically phosphorylated ( Eggert et al. , Eur. J. Biochem. 213 , 659-671 ) . The phenotype shows discontinuous and patch-like aggregates of the mutant protein in the nucleus . We suggest that phosphorylation of the site either regulates lamina assembly or lamina-chromatin interaction in interphase .