Abnormal Morphogenesis But Intact IKK Activation in Mice Lacking the IKKα Subunit of IκB Kinase

TLDR

The IκB kinase complex is composed of catalytic subunits IKKα and IKKβ and regulatory subunit IKKγ, and is thought to phosphorylate IκB inhibitors in response to proinflammatory signals, triggering their degradation and NF‑κB activation. The study examined the physiological role of IKKα by generating and analyzing IKKα‑deficient mice. IKKα is dispensable for IKK activation and IκB degradation, yet its absence disrupts morphogenetic processes such as limb and skeletal patterning and epidermal keratinocyte proliferation and differentiation.

Abstract

The oligomeric IκB kinase (IKK) is composed of three polypeptides: IKKα and IKKβ, the catalytic subunits, and IKKγ, a regulatory subunit. IKKα and IKKβ are similar in structure and thought to have similar function—phosphorylation of the IκB inhibitors in response to proinflammatory stimuli. Such phosphorylation leads to degradation of IκB and activation of nuclear factor κB transcription factors. The physiological function of these protein kinases was explored by analysis of IKKα-deficient mice. IKKα was not required for activation of IKK and degradation of IκB by proinflammatory stimuli. Instead, loss of IKKα interfered with multiple morphogenetic events, including limb and skeletal patterning and proliferation and differentiation of epidermal keratinocytes.