How overrated is phosphorylation? – an opinion
Posted by attilachordash on May 15, 2008
David Secko writes: “Today, it is thought that one third of the proteins present in a typical mammalian cell are covalently bound to phosphate (i.e. they are phosphorylated at one time or another)”
Well I haven’t checked what kind of measurement the above 1/3 estimation is based on but if true it is no wonder that phosphorylation is the almost constant subject of biological research. But if it is not true, then what’s the reason of the stardom?
I got one of my smartest comment to my Human proteome project: 21000 genes/1 protein, 10 years, $1 billion? from a scientist at the University if Rochester that could suggest an answer:
“Another example – we study protein phosphorylation and we think it’s important. Why? Because we can! We have methods and tools to measure it, but all along we have absolutely no evidence that phosphorylation is any more important than the hundred of other protein modifications that we know exist. There could be upwards of 1000 PTMs on every single protein, and we have the technology to accurately study about 5 of these.”
Neil said
Everyone cites that 1/3 of all proteins figure; I’ve done it myself and I don’t know the original source!
Try these from PubMed:
How do protein kinases recognize their substrates?
Kinomics: methods for deciphering the kinome.
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bill said
I read recently that there are hundreds of kinases (about 300?), but at least a thousand E3 ubiquitin ligases in a typical mammalian cell. That suggests that ubiquitination, for one, may be more important than phosphorylation. My guess is that this will turn out to be true, once we have the tools to study ubiquitination in detail (better probes for Ub-proteins, mutant Ub, etc etc).
Kay at Suicyte said
I cannot leave this uncommented
First, I do not think that the importance of phosphorylation is (too much) overrated. I would not build so much on this ‘1/3′ number, though, but rather on the number of genes/proteins dedicated to effecting, removing or recognizing phosphorylation. It is possible that the number of targets is both real and meaningful, but I am always wary that the number of targets (of anything) might include a high proportion of meaningless accidental modifications. I have talked about this concept of ‘not everything observed has to be meaningful’ in many of my own blog entries, e.g. with regard to alternative splicing and intragenic transcription. The same reasoning also applies to phosphorylation or, my favourite topic, ubiquitination.
@Bill: I think a current estimate for the human kinase complement is 517 active kinases, plus some 100 putative pseudogenes. As for ubiquitin E3s, my latest figure is 604 substrate recognition components (there are several E3 complexes consisting of some constitutive subunits plus one specificity factor). Both numbers are not carved into stone, I would expect them to increase slightly over the next decade. Nevertheless, we are in the same ballpark region for both modification types.
bill said
@Kay: huh. Now I want to find the review I (thought I) remembered those numbers from, and see whether the review or my memory was at fault. (The latter is more likely!)
Kay at Suicyte said
@Bill: Most people cite the review “The Protein Kinase Complement of the Human Genome” by G. Manning et al, in Science 298:1912-1934 (2002). A useful resource for the kinase figures can be found at http://kinase.com/human/kinome/
The ubiquitin figures are unpublished work from my group.