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Expression and Activity of the Signaling Molecules for Mitogen-Activated Protein Kinase Pathways in Human, Bovine, and Rat Lenses

¹From The Hormel Institute, University of Minnesota, Austin, Minnesota; and the ²Department of Molecular Biology, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey. ³Present affiliations: Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Genetics and The Penn Diabetes Center, University of Pennsylvania, Philadelphia, Pennsylvania; the ⁴Department of Pharmacology, University of Michigan, Ann Arbor, Michigan; and the ⁵Department of Molecular and Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island.

PURPOSE. The mitogen-activated protein kinase (MAPK) pathways play distinct roles in the lens. However, the expression patterns and activity levels of various components for these pathways have not been well-documented in vertebrate lenses, especially human lens. In the present study, the expressions and activities of extracellular signal-regulated kinase (ERK)-1/2/3, c-Jun NH2-terminal kinase (JNK)-1/2, p38 kinase, mitogen-activated protein kinase kinase (MEK)-1/2, and RAF1 were recorded in human, bovine, and rat lenses.

METHODS. Human, bovine, and rat lenses were isolated from intact eyes. The epithelia and different layers of fiber cells were isolated from these lenses. Total proteins extracted from these samples were subject to analysis of the expression patterns and activity levels of the MAPKs and the activating kinases of ERK1/2.

RESULTS. ERK1 and ERK2 were the most abundant MAPKs in terms of both protein and activity levels in all lenses. JNK1 and JNK2 were highly expressed in bovine lens, which differed from the pattern shared by human and rat lenses. p38 kinase was similarly expressed in bovine and rat lenses, but different from that in human lens. However, p38 kinase activity was exclusively detected in the epithelia. All lenses had MEK1/2 activity in their epithelia but the expression patterns of MEK1 and MEK2 differed in these lenses. RAF1 was expressed in the epithelia of all lenses, but its activity was detected only in rat lens.

CONCLUSIONS. ERK1 and ERK2 are the most abundant MAPKs in the ocular lens, providing the basis for their multiple functions in lens development and pathogenesis. The dominant epithelial distribution of JNK1/2 and p38 kinase suggests that the lens epithelium is a major site for stress response. ERK1, p38 kinase, and PKC can be used as molecular markers for aging.

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