Phospho-MEK1 (Thr292) Antibody [F18G17] Datasheet

Biological Description

Specificity	Phospho-MEK1 (Thr292) Antibody [F18G17] detects endogenous levels of total MEK1 protein only when it is phosphorylated at Thr292.
Background	Phospho‑MEK1 (Thr292) marks a key negative‑regulatory site on the dual‑specificity kinase MEK1, which sits at the core of the Raf–MEK–ERK MAPK cascade that controls cell proliferation, differentiation, and adhesion. MEK1 contains a proline‑rich insert and an activation loop phosphorylated at Ser217 and Ser221 by Raf‑family kinases, and in addition a regulatory segment encompassing Thr292 that lies outside the catalytic core but interfaces with MEK1–ERK2 and MEK1–PAK1 interactions. In active signaling, integrin‑ and growth‑factor‑driven PAK1 phosphorylates MEK1 at Ser298, which promotes MEK1–ERK2 complex formation and facilitates Raf‑1‑mediated activation of MEK1 by enhancing its encounter with upstream Raf and downstream ERK, thereby potentiating ERK‑dependent transcription and cytoskeletal remodeling. ERK‑dependent phosphorylation of MEK1 at Thr292 induces a negative feedback loop: ERK2‑mediated Thr292 phosphorylation reduces MEK1 kinase activity toward ERK1/2, interferes with MEK1 binding to ERK2, and attenuates PAK1‑dependent phosphorylation at Ser298, thereby dampening subsequent Raf‑mediated phosphorylation of the activation‑loop serines and curtailing the magnitude and duration of ERK signaling following cell‑adhesion events and mitogen stimulation. Thr292 phosphorylation functions as a temporal brake that tunes ERK output to mechanical cues and ECM engagement, and dysregulated MEK1 Thr292 phosphorylation has been implicated in perturbed feedback control of ERK in brain and tumor microenvironments.

Specificity

Phospho-MEK1 (Thr292) Antibody [F18G17] detects endogenous levels of total MEK1 protein only when it is phosphorylated at Thr292.

Background

Phospho‑MEK1 (Thr292) marks a key negative‑regulatory site on the dual‑specificity kinase MEK1, which sits at the core of the Raf–MEK–ERK MAPK cascade that controls cell proliferation, differentiation, and adhesion. MEK1 contains a proline‑rich insert and an activation loop phosphorylated at Ser217 and Ser221 by Raf‑family kinases, and in addition a regulatory segment encompassing Thr292 that lies outside the catalytic core but interfaces with MEK1–ERK2 and MEK1–PAK1 interactions. In active signaling, integrin‑ and growth‑factor‑driven PAK1 phosphorylates MEK1 at Ser298, which promotes MEK1–ERK2 complex formation and facilitates Raf‑1‑mediated activation of MEK1 by enhancing its encounter with upstream Raf and downstream ERK, thereby potentiating ERK‑dependent transcription and cytoskeletal remodeling. ERK‑dependent phosphorylation of MEK1 at Thr292 induces a negative feedback loop: ERK2‑mediated Thr292 phosphorylation reduces MEK1 kinase activity toward ERK1/2, interferes with MEK1 binding to ERK2, and attenuates PAK1‑dependent phosphorylation at Ser298, thereby dampening subsequent Raf‑mediated phosphorylation of the activation‑loop serines and curtailing the magnitude and duration of ERK signaling following cell‑adhesion events and mitogen stimulation. Thr292 phosphorylation functions as a temporal brake that tunes ERK output to mechanical cues and ECM engagement, and dysregulated MEK1 Thr292 phosphorylation has been implicated in perturbed feedback control of ERK in brain and tumor microenvironments.

Usage Information

Application

WB, IP

Dilution

WB	IP
1:1000	1:50

Reactivity

Human, Mouse, Rat

Source

Rabbit Monoclonal Antibody

MW

45 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/27342992/
https://pubmed.ncbi.nlm.nih.gov/25971971/

Application Data

WB

Validated by Selleck

Lane 1: MDA-MB-231, Lane 2: C6, Lane 3: C6 (phosphatase treated), Lane 4: NIH/3T3