Cloning and characterization of mPAL, a novel Shc SH2 domain-binding protein expressed in proliferating cells

Shc adaptor proteins play a role in linking activated cell surface receptor s to the Ras signaling pathway in response to receptor mediated tyrosine ki nase activation. While the function of Shc in the activation of the Ras pat hway, ia binding to Grb2 has been well characterized, it is becoming increa singly apparent that Shc participates in additional signaling pathways thro ugh interactions with other cytoplasmic proteins. Using the yeast two-hybri d system, we have identified a unique She binding protein designated PAL (P rotein expressed in Activated Lymphocytes) with no similarity to other know n proteins. mPAL binds specifically to the Shc SH2 domain and unlike previo usly described Shc SH2 domain-protein interactions, the association of mPAL and She is phosphotyrosine-independent. RNA and protein expression are res tricted to tissues containing actively dividing cells and proliferating cel ls in culture, mPAL expression is induced upon growth factor stimulation an d is down-regulated upon growth inhibition. This pattern, and timing of mPA L expression and its association with the She adaptor molecule suggests a r ole for this protein in signaling pathways governing cell cycle progression .