ABSTRACT
I. Introduction 313
II. Detecting Protein Interactions in Intact Cells and Animals 315
A. Two-Hybrid 315
B. Protein-Fragment Complementation 317
C. Other Strategies 319
III. Applications In Vivo 321
IV. Concluding Comments 322
Acknowledgments 323
References 323
I. Introduction
Refinement of the human genome is expected to facilitate investigations into
normal physiology and disease processes, leading to discovery of targets for
new medical therapies and drugs (1). However, regulation of gene expression,
posttranslational modifications of proteins (e.g., phosphorylation or myristoyla-
tion), or interactions between proteins cannot be deduced or inferred from
DNA sequences (2). Thus, a biological function has been assigned to only a
small portion of the genome. The vast amount of available sequence data has pro-
duced a demand for tools to integrate these data into the complex physiology of
whole organisms (3). To determine the function of a particular protein within its
cellular context, researchers are developing and applying several different tech-
niques for identifying and characterizing protein function and interactions in vivo.
