Phosphorylations of alpha A- and alpha B-crystallin.

In addition to being refractive proteins in the vertebrate lens, the two alpha-crystallin polypeptides (alpha A and alpha B) are also molecular chaperones that can protect proteins from thermal aggregation. The alpha B-crystallin polypeptide, a functional member of the small heat shock family, is expressed in many tissues in a developmentally regulated fashion, is stress-inducible, and is overexpressed in many degenerative diseases and some tumors indicating that it plays multiple roles. One possible clue to alpha-crystallin functions is the fact that both polypeptides are phosphorylated on serine residues by cAMP-dependent and cAMP-independent mechanisms. The cAMP-independent pathway is an autophosphorylation that has been demonstrated in vitro, depends on magnesium and requires cleavage of ATP. Disaggregation of alpha A-, but not alpha B-crystallin into tetramers results in an appreciable increase in autophosphorylation activity, reminiscent of other heat shock proteins, and suggests the possibility that changes in the aggregation state of alpha A-crystallin are involved in yet undiscovered signal transduction pathways. The alpha-crystallin polypeptides differ with respect to their abilities to undergo cAMP-dependent phosphorylation, with preference given to the alpha B-crystallin chain. These differences and complexities in alpha-crystallin phosphorylations, coupled with the differences in expression patterns of the two alpha-crystallin polypeptides, are consistent with the idea that each polypeptide has distinctive structural and metabolic roles.