"Heads and tails" of intermediate filament phosphorylation: multiple sites and functional insights.
Intermediate filaments (IFs) are major components of the mammalian cytoskeleton. They are among the most abundant cellular phosphoproteins; their phosphorylation typically involves multiple sites at repeat or unique motifs, preferentially within the "head" or "tail" domains. Phosphorylation and dephosphorylation are essential for the regulation of IF dynamics by modulating the intrinsic properties of IFs: solubility, conformation and filament organization, and, in addition, for the regulation of other IF post-translational modifications. These phosphorylation-regulated properties dictate generalized and context-dependent IF functions that reflect their tissue-specific expression. Most important among IF phosphorylation-mediated functions are the regulation of IF cellular or subcellular compartmentalization, levels and turnover, binding with associated proteins, susceptibility to cell stresses (including apoptosis), tissue-specific functions and IF-associated disease pathogenesis (where IF hyperphosphorylation also serves as a tissue-injury marker).
Omary
M Bishr
MB
Department of Medicine, Palo Alto VA Medical Center and Stanford University School of Medicine, 3801 Miranda Avenue, Palo Alto, CA 94304, USA. mbishr@stanford.edu
Ku
Nam-On
NO
Tao
Guo-Zhong
GZ
Toivola
Diana M
DM
Liao
Jian
J
D000818:Animals; D002451:Cell Compartmentation; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007382:Intermediate Filaments / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000502:physiology*
D007381:Intermediate Filament Proteins