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).
Bibliographical noteFunding Information:
We are grateful to Pierre Coulombe, Ralph Nixon and Harish Pant for their reading of and suggestions on the review before submission, and to Kris Morrow for figure preparation. We also thank current and prior laboratory members who have made essential contributions to our work on keratin phosphorylation during the past 15 years, including Chih-Fong Chou, Li Feng, Lori Lowthert, Evelyn Resurreccion, Carrie Riopel, Qin Zhou and Xiangjun Zhou. Our work is supported by a Department of Veterans Affairs Merit Award, and NIH grants DK47918 and DK52951 (M.B.O.). We apologise for not being able to cite all potentially relevant references owing to space constraints. M.B.O. is indebted to Tony Hunter and Ian Trowbridge for their mentorship in studies pertaining to protein phosphorylation.
All Science Journal Classification (ASJC) codes
- Molecular Biology