Abstract: Extracellular-signal regulated kinase (ERK) signaling is required for a multitude of physiological and patho-physiological processes. However, the identities of the proteins that ERK phosphorylates to elicit these responses are incompletely known. Using an affinity purification methodology of general utility, here we identify cytoplasmic dynein intermediate chain 2 (DYNC1I-2, IC-2) as a novel substrate for ERK following epidermal growth factor receptor stimulation of fibroblasts. IC-2 is a subunit of cytoplasmic dynein, a minus-end directed motor protein necessary for transport of diverse cargos along microtubules. Emerging data support the hypothesis that post-translational modification regulates dynein but the signaling mechanisms used are currently unknown. We find that ERK phosphorylates IC-2 on a novel, highly conserved Serine residue proximal to the binding site for the p150Glued subunit of the cargo adapter dynactin. Surprisingly, neither constitutive phosphorylation nor a phosphomimetic substitution of this Serine influences binding of p150Glued to IC-2. These data suggest that ERK phosphorylation of IC-2 regulates dynein function through mechanisms other than its interaction with dynactin.
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Pullikuth, A.K.; Ozdemir, A.; Cardenas, D.; Bailey, E.; Sherman, N.E.; Pfister, K.K.; Catling, A.D. Epidermal Growth Factor Stimulates Extracellular-Signal Regulated Kinase Phosphorylation of a Novel Site on Cytoplasmic Dynein Intermediate Chain 2. Int. J. Mol. Sci. 2013, 14, 3595-3620.
Pullikuth AK, Ozdemir A, Cardenas D, Bailey E, Sherman NE, Pfister KK, Catling AD. Epidermal Growth Factor Stimulates Extracellular-Signal Regulated Kinase Phosphorylation of a Novel Site on Cytoplasmic Dynein Intermediate Chain 2. International Journal of Molecular Sciences. 2013; 14(2):3595-3620.
Pullikuth, Ashok K.; Ozdemir, Aysun; Cardenas, Daviel; Bailey, Evangeline; Sherman, Nicholas E.; Pfister, K. K.; Catling, Andrew D. 2013. "Epidermal Growth Factor Stimulates Extracellular-Signal Regulated Kinase Phosphorylation of a Novel Site on Cytoplasmic Dynein Intermediate Chain 2." Int. J. Mol. Sci. 14, no. 2: 3595-3620.