50. You are studying how phosphorylation by the Cdc2 kinase controls nuclear lam

Question

50. You are studying how phosphorylation by the Cdc2 kinase controls nuclear lamina disassembly during mitosis. You make a series of mutations in a gene encoding a lamin protein and express these mutated lamins inside the cell (ie the cell now makes the mutated lamins). You find that when you mutate a serine residue on the amino terminal domain of the nuclear lamin, the mutated protein assembles into the nuclear
lamina just fine, but does not depolymerize during mitosis. Suggest a possible reason why this lamin protein might be resistant to Cdc2 kinase-mediated disassembly.

Explanation / Answer

Suggest a possible reason why this lamin protein might be resistant to Cdc2 kinase-mediated disassembly.

The extracellular domain serves as the ligand-binding part of the molecule. It can be a separate unit that is attached to the rest of the receptor by a disulfide bond. The same mechanism can be used to bind two receptors together to form a homo- or heterodimer. The transmembrane element is a single helix. The intracellular or cytoplasmic domain is responsible for the (highly conserved) kinase activity, as well as several regulatory functions.

During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are - like you said - thought to be involved in nuclear stability.

But, remember: Phosphorylation activates or deactivates many protein enzymes

This lamin protein might have seen its phosphorylation process mutated to deactive - NOT activate - the correct proteins for nuclear stability and assembly.

How?

Upon the deactivating signal, the protein becomes dephosphorylated again and stops working. This is the mechanism in many forms of signal transduction, for example the way in which incoming light is processed in the light-sensitive cells of the retina.

Bottom line: the kinase mutated and signaled DEPHOSPHYRYLATION, not phosphorylation - aka deactivation of the proteins. aka catastrophe!

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