Question

Does phosphorylation of a signaling protein by an upstream kinase represent a signaling input or output? Explain.

Answer 1

Signaling pathway together form a network that connect receptors to different cellular components.   Such networks receive and process the signals. In all signaling pathways information flow through coupled biochemical reactions and interactions molecular components that control the output.

One of such reaction is phosphorylation of the downstream effectors by a kinase, the phosphorylation of effectors leads to the downstream signaling and finally giving output. Most of the signal transduction pathway involves the kinase , which sometimes interconnect different signaling cascade and leads to different function. Most signaling pathways in mammalian cells interact with one another. This so-called “crosstalk” starts at the level of receptors. Growth factor receptors with intrinsic tyrosine kinase activity, for example, interact with multiple effector pathways, including the Ras-ERK-kinase pathway, the phosphoinositide 3-kinase (PI3K) pathway, and the phospholipase-C γ pathway.

Signaling pathways, most of the time exhibit a Positive-feedback loops. For example, the ERK and phospholipase A2 interaction (PLA2), which results in the activation of PLA2 (probably via activation of MNK1/2, which phosphorylates PLA2 at S727), leading to the increased production of arachidonic acid. Diacylglycerol and arachidonic acid together can activate protein kinase C (PKC). This positive-feedback loop results in prolonged activation of PKC as well as ERK. Such positive-feedback loops can function as switches to move the signaling network from an inactive to persistently active state.

Most of the protein kinases phosphorylate multiple transcription factors, The JNK and p38 MAP kinases and the transcription factors ATF2 and Elk1. This crisscrossing allows a cell to integrate multiple signals to give a cohesive pattern of gene expression. In the case of Elk1 and ATF2, for example, the motif enables upstream kinases to effectively synchronize the activity levels of the transcription factors means giving output.

So we can conclude from the examples that the phosphorylation by kinase always results in output.

One another example is given below.

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