SH2 domain structure and function.
An emerging theme in both the biology of signal transduction and the biochemistry of proteins has been the modular function of small protein domains. In some cases these can directly regulate catalytic activity. In others, they serve to interconnect important regulatory proteins. SH2 (src homology 2) domains represent some of the best studied models. Originally identified on the basis of homology in src and fps [1], SH2s are elements that ordinarily respond to tyrosine phosphorylation by binding the phosphorylated sequence. As such, they are key elements in tyrosine kinase regulation of cellular processes. Because SH2 interactions result from phosphorylation, such elements provide a regulatable circuitry along which signals can be transmitted in a timely manner. Because the regulation is based on a common mechanism, signal generators can target several different proteins coordinately. The PDGF receptor (PDGFr), for example, may interact with as many as ten different elements [2,3]. There are a number of excellent reviews on SH2 domains available [4-11]. This discussion will try to show how genetic, biochemical and biophysical results can be integrated in a satisfying way.
Schaffhausen
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Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry
D000952:Antigens, Polyomavirus Transforming; D011506:Proteins; D016392:Proto-Oncogene Proteins pp60(c-src)