Rous sarcma virus (RSV) carries an oncogene called Src, which encodes an active
ID: 32555 • Letter: R
Question
Rous sarcma virus (RSV) carries an oncogene called Src, which encodes an active tyrosine kinase that phosphorylates something else and causes unchecked cell proliferation. Normally Src carreis an attached fatty acid called myristoylate, which in turn binds to the cytoplasmic side of the phospholipid membrane. A mutant version of the same Src seems to be spread evenly around the cell. The mutant form does not bind to the phospholipid membrane. When you infect cells with BOTH the normal (wildtype) and the mutant, both RSV proteins are produced.
a. What is the relative concentration of normal Src to mutant Scr just inside the membrane? Near the nucleus?
b. The target for Src phosphorylation is stuck in the membrane. Briefly explain why the mutant Src does not cause cell proliferation?
Explanation / Answer
a)
A function for Src tyrosine kinases in normal cell growth was first demonstrated with the binding of family member p56lck to the cytoplasmic tail of the CD4 and CD8 co-receptors on T-cells. Src tyrosine kinases also transmit integrin-dependent signals central to cell movement and proliferation. Hallmarks of v-Src induced transformation are rounding of the cell and the formation of actin rich podosomes on the basal surface of the cell. These structures are correlated with increased invasiveness, a process thought to be essential for metastasis. Thus, the concentration of normal Src relative to mutant Src in high near the membrane and low near the nucleus.
b)
v-Src lacks the C-terminal inhibitory phosphorylation site (tyrosine-527), and is therefore constitutively active as opposed to normal Src (c-Src) which is only activated under certain circumstances where it is required (growth factor signaling). v-Src is therefore an instructive example of an oncogene whereas c-Src is a proto-oncogene. When the Src gene does not undergo phosphorylation it does not get activated and hence the mutant version of Src does not cause cell proliferation.
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