The Src protein functions as a tyrosine kinase
The first clues to how cell-to-cell signaling via growth factors operates came from biochemical analysis of the v-src oncogene
The trail of clues led, step-by-step, from this protein to the receptors used by cells to detect growth factors
and to the intracellular signaling pathways that control normal and malignant cell proliferation.
The v-src encoded oncoprotein
This was the first cellular oncoprotein to be studied
The encoded protein was made as a polypeptide chain of 533 amino acid residues and had a mass of almost precisely 60 kilo daltons (kD).
Avian and mammalian cells transformed by the v-src oncogene
exhibit a radically altered shape
pump in glucose from the surrounding medium
grow in an anchorage-independent fashion
lose contact inhibition, and to form tumors.
How did Src affect a wide variety of cellular targets ????
Src has a kinase activity
Phosphorylation involves the covalent attachment of phosphate groups to the side chains of specific amino acid residues.
Hence, it was clear that Src operates as a protein kinase
an enzyme that removes a high-energy phosphate group from ATP and transfers it to a suitable protein substrate
These early experiments suggested that its usual mode of action also involved the phosphorylation of certain target proteins within cells.
Src has a kinase activity
Src was itself a phosphoprotein
It also carried phosphate groups attached covalently to one or more of its amino acid side chains.
This indicated that Src served as a substrate for phosphorylation by a protein kinase
either phosphorylating itself (autophosphorylation) or serving as the substrate of yet another kinase.
The fact that Src functions as a kinase was a major revelation.
In principle, a protein kinase can phosphorylate multiple, distinct substrate proteins within a cell.
More than 50 distinct Src substrates are known
Once phosphorylated, each of these substrate proteins may be functionally altered and proceed, in turn, to alter the functions of its own set of downstream targets.
Src is different from all other protein kinases uncovered previously.
These other kinases were known to attach phosphate groups to the side chains of
serine and threonine amino acid residues.
Src, in contrast, phosphorylated certain tyrosine residues of its protein substrates
Src succeeds in transforming cells through its ability to act as a tyrosine kinase (TK)
Src is a tyrosine kinase (TK)
4 окт 2024