Hi Niloy Kumar Das,

Cells may need to respond to several signals at once, and different cells may need to respond to the same signal in different ways. All this is made possible because the mechanism for detection of a signal is not directly coupled to the response, but is separated by a chain of signaling events. This principle allows signaling systems to be highly flexible. Exemplifying the very meaning of upstream & downstream effectors in cell signaling cascades, lets consider, in a nutshell, the mitogen-activated protein (MAP) kinase (MAPK) cascades, which contain UPSTREAM MAP4K and DOWNSTREAM MAP kinase-activated kinase, MAPKAPK.  That constitutes a large family of serine/threonine kinases that are involved in a wide range of signal transduction cascades. This large family of kinases has been organized into four distinct MAPK cascades named according to the MAPK component that is the central enzyme of each of the cascades. These four MAPK cascades are the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and ERK5 cascades. Each of these four cascades is in turn comprised of a core component that consists of three tiers of protein kinases termed MAPK, MAPKK, and MAP3K (MAPKKK). In several cases the cascade contains two additional tiers consisting of an UPSTREAM MAP4K and a DOWNSTREAM MAP kinase-activated kinase;). Signal transduction triggered by each cascade involves the sequential phosphorylation and activation of the components in the subsequent tiers. The MAPK signal transduction cascades involve the coordination of a variety of extracellular signals that are initiated to control diverse cellular processes such as proliferation, differentiation, survival, development, stress response, and apoptosis. The entirety of the MAPK systems involves nearly 70 individual genes which, due to alternative splicing events, generates a highly complex system of signaling molecules that includes over 200 proteins. The MAPK signaling cascades are most often initiated by receptor-mediated activation of members of the small monomeric G protein family such as Ras, Rac or Rho. In addition, the MAPK cascades can activate UPSTREAM components via their interactions with adaptor proteins. The initial signals are then propagated to DOWNSTREAM proteins of the three to five tiers of the four MAPK cascades. The kinases in each tier phosphorylate and activate the kinases located in the next tier downstream. This process is repeated from tier to tier allowing for rapid and regulated transmission of the original initiating signal. As indicated above, the MAPK, MAPKK and MAP3K tiers are core components of all MAPK cascades.

Best wishes,

Ilya Tsyrlov

If you study signalling mechanism of kinase/ specific protein (such as X protein), then upstream effector is  a protein which either activates or deactivates protein X (via phosphorylation or dephosphorylation) . Moreover, protein X regulates downstream molecules in the studied signalling pathway either through activation or deactivation. Furthermore, you can have a look on KEGG databases to find downstream/upstream molecules of desired pathway.   

Hi Niloy Kumar Das,

Cells may need to respond to several signals at once, and different cells may need to respond to the same signal in different ways. All this is made possible because the mechanism for detection of a signal is not directly coupled to the response, but is separated by a chain of signaling events. This principle allows signaling systems to be highly flexible. Exemplifying the very meaning of upstream & downstream effectors in cell signaling cascades, lets consider, in a nutshell, the mitogen-activated protein (MAP) kinase (MAPK) cascades, which contain UPSTREAM MAP4K and DOWNSTREAM MAP kinase-activated kinase, MAPKAPK.  That constitutes a large family of serine/threonine kinases that are involved in a wide range of signal transduction cascades. This large family of kinases has been organized into four distinct MAPK cascades named according to the MAPK component that is the central enzyme of each of the cascades. These four MAPK cascades are the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and ERK5 cascades. Each of these four cascades is in turn comprised of a core component that consists of three tiers of protein kinases termed MAPK, MAPKK, and MAP3K (MAPKKK). In several cases the cascade contains two additional tiers consisting of an UPSTREAM MAP4K and a DOWNSTREAM MAP kinase-activated kinase;). Signal transduction triggered by each cascade involves the sequential phosphorylation and activation of the components in the subsequent tiers. The MAPK signal transduction cascades involve the coordination of a variety of extracellular signals that are initiated to control diverse cellular processes such as proliferation, differentiation, survival, development, stress response, and apoptosis. The entirety of the MAPK systems involves nearly 70 individual genes which, due to alternative splicing events, generates a highly complex system of signaling molecules that includes over 200 proteins. The MAPK signaling cascades are most often initiated by receptor-mediated activation of members of the small monomeric G protein family such as Ras, Rac or Rho. In addition, the MAPK cascades can activate UPSTREAM components via their interactions with adaptor proteins. The initial signals are then propagated to DOWNSTREAM proteins of the three to five tiers of the four MAPK cascades. The kinases in each tier phosphorylate and activate the kinases located in the next tier downstream. This process is repeated from tier to tier allowing for rapid and regulated transmission of the original initiating signal. As indicated above, the MAPK, MAPKK and MAP3K tiers are core components of all MAPK cascades.

Best wishes,

Ilya Tsyrlov