Effect of catalytically active recruited crystallins on lens metabolism

Reddy, M. Chandra Sekhar; Groth-Vasselli, Barbara; Sharon, Ashwini; Farnsworth, Patricia N.

doi:10.1016/0014-5793(93)80748-j

Cited by 1 publication

(1 citation statement)

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“…A partial similarity with the ATP binding site for these kinases was found for aB. Evidence for ATP binding by a-crystallin has been reported (63).…”

Section: Discussionmentioning

confidence: 75%

Alpha-crystallin/small heat shock protein has autokinase activity.

Kantorow

Piatigorsky

1994

Proc. Natl. Acad. Sci. U.S.A.

124

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The a-crystallins (aA and aB) are major water-soluble proteins of the transparent eye lens that are expressed in a variety of tissues and can function as molecular chaperones. aB-crystallin is also a small heat shock protein assocated with numerous degenerative diseases and abnormal growth patterns. Previous experiments have shown that aAand aB-crystallin are phosphorylated on specific serine residues by a cAMP-dependent pathway. Here (3,4) and the latter belonging to a superfamily of microbial stress proteins (5). In addition, different taxon-specific crystallins also present in the lenses of many individual species are related or identical to metabolic enzymes (1,6,7). The enzyme-crystallins may retain enzymatic activity in the lens, as they do in non-lens tissues. The dual use of the same protein as a refractive lens crystallin and a functional enzyme or stress protein has been called gene sharing (6).The two a-crystallins (aA and aB) are present in all vertebrate lenses and are the major proteins of the human lens. aA and aB are encoded in separate genes which have different patterns of regulation (8). Although present principally in the lens, aA (9, 10) and aB (11,12) are also expressed to varying extents in different non-lens tissues, can function as molecular chaperones (13,14), and can complex with shsps (15, 16). Indeed, aB-crystallin is a functional shsp and is inducible by heat and other physiological stresses (4,(17)(18)(19). aB-crystailin/ shsp has been associated with changes in cellular morphology during embryogenesis (20,21) and with numerous pathologies, including neurodegenerative diseases (22)(23)(24)(25)(26)(27)(28)(29), fibroblasts from patients with Werner disease (30), harmatomas (31), and neuroectodermal tumors (32) (see refs. 8 and 33 for reviews).The a-crystallin polypeptides undergo many posttranslational modifications (see ref. 13 for references). One of these is phosphorylation of specific serine residues, which can occur by a cAMP-dependent pathway in lens extracts (34-36). Here we provide evidence that both the aA and aB polypeptides of the bovine lens can autophosphorylate in the absence of cAMP. The finding that the a-crystallin polypeptides have autokinase activity suggests that these ubiquitous refractive/ shsp/molecular chaperone proteins have a metabolic as well as a structural role in the normal lens and other tissues. MATERIALS AND METHODSPreparation of the Lens Extract and a-Crysns. Bovine lenses and a-crystallin preparations were a gift of Joseph Horwitz (Jules Stein Eye Institute, University of California, Los Angeles, School of Medicine). All preparations were stored at -800C. Extracts of the outer cortex of the lenses were prepared as described (37). The a-crystallins were prepared from the outer cortex ofbovine lenses (13). In brief, total a-crystallin was purified by gel filtration on a Sephacryl S-200 column followed by FPLC purification on a Superose 6 HR 10/30 prepacked column; the aA and aB polypeptides were obtained by use of a Bio-Rad Rotofor prepara...

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“…A partial similarity with the ATP binding site for these kinases was found for aB. Evidence for ATP binding by a-crystallin has been reported (63).…”

Section: Discussionmentioning

confidence: 75%