title: Phosphorylation of αB-crystallin: Role in stress, aging and patho-physiological conditions.
abstract: BACKGROUND
  αB-crystallin, once thought to be a lenticular protein, is ubiquitous and has critical roles in several cellular processes that are modulated by phosphorylation. Serine residues 19, 45 and 59 of αB-crystallin undergo phosphorylation. Phosphorylation of S45 is mediated by p44/42 MAP kinase, whereas S59 phosphorylation is mediated by MAPKAP kinase-2. Pathway involved in S19 phosphorylation is not known.
  
  
  METHODS
  The review highlights the role of phosphorylation in (i) oligomeric structure, stability and chaperone activity, (ii) cellular processes such as apoptosis, myogenic differentiation, cell cycle regulation and angiogenesis, and (iii) aging, stress, cardiomyopathy-causing αB-crystallin mutants, and in other diseases.
  
  
  CONCLUSIONS
  Depending on the context and extent of phosphorylation, αB-crystallin seems to confer beneficial or deleterious effects. Phosphorylation alters structure, stability, size distribution and dynamics of the oligomeric assembly, thus modulating chaperone activity and various cellular processes. Phosphorylated αB-crystallin has a tendency to partition to the cytoskeleton and hence to the insoluble fraction. Low levels of phosphorylation appear to be protective, while hyperphosphorylation has negative implications. Mutations in αB-crystallin, such as R120G, Q151X and 464delCT, associated with inherited myofibrillar myopathy lead to hyperphosphorylation and intracellular inclusions. An ongoing study in our laboratory with phosphorylation-mimicking mutants indicates that phosphorylation of R120GαB-crystallin increases its propensity to aggregate.
  
  
  CONCLUSIONS
  Phosphorylation of αB-crystallin has dual role that manifests either beneficial or deleterious consequences depending on the extent of phosphorylation and interaction with cytoskeleton. Considering that disease-causing mutants of αB-crystallin are hyperphosphorylated, moderation of phosphorylation may be a useful strategy in disease management. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Raman
authors.initials: R
authors.lastname: Bakthisaran
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Kranthi Kiran
authors.initials: KK
authors.lastname: Akula
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Tangirala
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. Electronic address: mohan@ccmb.res.in.
authors.forename: Ch Mohan
authors.initials: ChM
authors.lastname: Rao
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008954:Models, Biological; D009135:Muscular Diseases / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D013312:Stress, Physiological; D013329:Structure-Activity Relationship
chemical_list: C511246:CRYAA protein, human; D003459:Crystallins
keywords: AlphaB-crystallin; Desmin-related myopathy; Molecular chaperone; Phosphorylation; Small heat shock protein; Stress, aging and diseases