TNK1
TNK1 (thirty-eight-negative kinase 1, also KOS1) is a non-receptor tyrosine kinase belonging to the Ack family. It contains a truncated kinase domain at the N-terminus followed by a CRIB-like motif and proline-rich regions that mediate interactions with Grb2 and other signaling proteins. TNK1 becomes activated during embryogenesis and by cytokine stimulation, and phosphorylation-dependent degradation keeps its expression low in adult tissues. In contrast to many kinases, TNK1 functions predominantly as a tumor suppressor: knockout mice develop spontaneous tumors, and TNK1 loss-of-function mutations and epigenetic silencing occur in human lymphomas and carcinomas, where unrestrained Ras signaling promotes transformation. Its suppression of the Ras-MAPK pathway via Grb2-Sos sequestration defines a distinctive inhibitory role among tyrosine kinases.
