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Biological Regulation by Protein Phosphorylation
Protein
Protein
P
Receptor
Receptor
Response to
extracellular signal
Protein kinase
Protein phosphatase
Ion
channel
Second messenger
Neurotransmitter,
hormone or growth factor
Intracellular
Extracellular
Fig. 4
Protein phosphorylation is a common mechanism used to transduce extracellular
stimuli into intracellular responses. Extracellular molecules bind to their cell surface receptors
and activate protein kinases or phosphatases. Some kinases and phosphatases are intrinsic
components of receptors and are directly activated by ligand binding. Others are activated,
either directly or indirectly, by changes in the levels of second messengers such as cAMP,
cGMP, diacylglycerol, and Ca
2
+
. The activity of some kinases and phosphatases are regulated
by other kinases and phosphatases as part of a phosphorylation cascade. (ModiFed from Scott
and Patel, Encyclopedia of Human Biology (1991) 6; 201–211; reproduced by permission of
Academic Press.)
have revealed three distinct superfamilies
of phosphatases; two families of protein
serine/threonine phosphatases (PPP and
PPM families) and one protein tyrosine
phosphatase family (PTP). Within the PTP
family is a subgroup of enzymes that
dephosphorylate both tyrosine and ser-
ine/threonine residues: this group is called
the
dual-specifcity phosphatases
.
Thirty-two protein-serine/threonine ph-
osphatase genes have been identiFed in the
human genome sequence. The enzymes
encoded by these genes are responsible
for dephosphorylating proteins that are
acted upon by over 500 serine/threonine
kinases. Thus, it is very likely that most
serine/threonine phosphatases will have
multiple substrates. In most cases, the cat-
alytic subunits of these phosphatases are
capable of binding to numerous regulatory
and targeting subunits. These auxiliary
subunits are expressed in cell-type spe-
ciFc patterns and can be located within
different regions of the cell. They regulate
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