The protein encoded by MPL is a receptor for thrombopoietin (TPO-R). Thrombopoietin is the major regulator of megakaryocytopoiesis and platelet formation. Upon binding of thrombopoietin TPO-R is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated.
Somatic MPL mutations (essentially missense substitutions) have been found exclusively in haematopoietic and lymphoid tissue tumors. These mutations are observed in a region corresponding to aminoacids 505-519, with a hot spot at aminoacid 515
References (open access):
Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Tefferi A.Leukemia. 2010 Jun;24(6):1128-38.