摘要：

The Ras-dependent activation of mitogen-activated protein (MAP) kinase pathways by many receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) requires the activation of Src family tyrosine kinases. Stimulation of 尾adrenergic receptors resulted in the assembly of a protein complex containing activated c-Src and the receptor. Src recruitment was mediated by 尾-arrestin, which functions as an adapter protein, binding both c-Src and the agonist-occupied receptor. 尾-Arrestin 1 mutants, impaired either in c-Src binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of 尾adrenergic receptor鈥搈ediated activation of the MAP kinases Erk1 and Erk2. These data suggest that 尾-arrestin binding, which terminates receptor鈥揋 protein coupling, also initiates a second wave of signal transduction in which the 鈥渄esensitized鈥receptor functions as a critical structural component of a mitogenic signaling complex.

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