Association of leukocyte surface receptors with protein kinases

Abstract

Signalling through most leukocyte surface receptors is based on ligation-induced activation of the protein tyrosine kinases associated with the receptors' intracellular domains. The activated kinases phosphorylate specific cytoplasmic proteins involved in propagation of the signalling cascade which leads to ultimate cellular responses such as induction of gene transcription followed by proliferation, apoptosis, and execution of various effector functions. Some receptors possess intracellular domains with intrinsic kinase activity (e.g. insulin receptor; transforming growth factor receptor). Many leukocyte surface receptors (e.g. T-cell receptor, B-cell receptor, Fc receptors) are noncovalently associated with cytoplasmic protein tyrosine kinases of the Src family. Most cytokine receptors are associated with protein tyrosine kinases of the Jak family which phosphorylate and thereby activate transcription factors of the STAT family. Receptors anchored in the membrane via a glycolipid (glycosylphosphatidylinositol) moiety are linked to intracellular kinases within membrane microdomains of specific lipid composition which may include so far poorly known transmembrane linker proteins. A number of diseases have been identified which are caused by defective or dysregulated receptor-linked protein kinases or by defects in the receptor-kinase interaction. Therefore receptor-associated kinases may be potential targets for therapeutic intervention.