The proto oncogene c CBL was initially identified as the cellular homologue of v CBL oncogene that induces pre B cell lymphomas and myeloid leukemias in mice. In more recent studies CBL has been shown to be a negative regulator of tyrosine kinase signaling. The ubiquitin ligase activity of CBL leads to the degradation of tyrosine kinases, thus attenuating the signal of receptors. Targets of CBL include activated protein tyrosine kinases belonging to the Src and Syk/Zap 70 families. An additional mechanism to attenuate receptor signaling is thought to be achieved by CBL’s interaction with downstream targets of tyrosine kinases, such as PI 3K and Vav.