Nuclear tyrosine phosphorylation: The beginning of a map

Tyrosine phosphorylation is usually associated with cytoplasmic events. Yet , over the years, many reports have accumulated on tyrosine phosphorylation of individual molecules in the nucleus, and several tyrosine kinases and p hosphatases have been found to be at least partially nuclear. The question arises as to whether nuclear tyrosine phosphorylation represents a collecti on of loose ends of events originating in the cytoplasm or if there may be intranuclear signaling circuits relying on tyrosine phosphorylation to regu late specific processes. The recent discovery of a mechanism causing nuclea r tyrosine phosphorylation has prompted us to review the cumulative evidenc e for nuclear tyrosine phosphorylation pathways and their possible role. Wh ile we found that no complex nuclear function has yet been shown to rely up on intranuclear tyrosine phosphorylation in an unambiguous fashion, we foun d a very high number of compelling observations on individual molecules tha t suggest underlying networks linking individual events. A systematic prote omics approach to nuclear tyrosine phosphorylation should help chart possib le interaction pathways. BIOCHEM PHARMACOL 60;8:1203-1215, 2000. (C) 2000 E lsevier Science Inc.