ARE PHOSPHORYLATED TYROSINE RESIDUES OF CERTAIN RECEPTORS INVOLVED ININDUCING TRANSITORY COVALENT PROTEIN CROSS-LINKING

Following ligand binding a number of cell-surface receptors become pho sphorylated at tyrosine residues of their cytosolic domains. These pho sphorylations are associated with initiation of a signalling programme involving a sequence of tyrosine-phosphorylated protein-protein inter actions. In the recognition process between phosphorylated proteins, e lectrostatic interactions between negatively charged phosphorylated ty rosines, serine and threonine residues and positively charged lysines play an important role as well as hydrophobic and H-bonding reactions. We suggest in this paper that the fairly high-energy phosphate bond o f certain protein phosphorylated tyrosines are possibly involved in in ducing transitory protein cross-linking reactions. Through a process i nvolving transfer of an activated phosphate of phosphorylated tyrosine to a side-chain carboxyl group of the receptor or next protein of the signalling sequence, an acyl phosphate is formed. This then acylates a hydroxyl group on a serine, threonine or tyrosine residue of the pro tein not carrying the carboxyl phosphate to give an ester linkage, thu s cross-linking the two proteins of the signalling pathway. The covale nt ester linkage is labile to hydrolysis and depending on the protein- protein molecular environment it might have a finite half-life. On hyd rolysis, the transitory covalent linkage is broken with separation of the proteins. It is suggested therefore that formation of a protein-pr otein ester linkage introduces a type of timing device into the system . Breakdown of the original protein-phosphorylated tyrosine in this ca se therefore does not involve a phosphatase enzyme.