Related Experiment Video

Updated: May 7, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

EGFR/MEK/ERK/CDK5-dependent integrin-independent FAK phosphorylated on serine 732 contributes to microtubule

K Rea1, M Sensi, A Anichini

  • 1Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

Cell Death & Disease
|October 5, 2013
PubMed

Insights

Focal adhesion kinase (FAK) phosphorylation on serine 732 (P-FAKSer732) is crucial for tumor cell mitosis and microtubule dynamics, offering a new therapeutic target in cancers with active EGFR/MEK/ERK/CDK5 signaling.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in cell migration and proliferation.
  • While tyrosine phosphorylations of FAK are well-studied, the roles of serine phosphorylations remain unclear.
  • Serine 732 phosphorylation (P-FAKSer732) levels vary in tumor cells and its function is not fully understood.

Purpose of the Study:

  • To investigate the role of FAK phosphorylation on serine 732 (P-FAKSer732) in cancer cell proliferation and mitosis.
  • To elucidate the relationship between P-FAKSer732, microtubule dynamics, and specific signaling pathways.
  • To identify P-FAKSer732 as a potential therapeutic target in neoplastic cells.

Main Methods:

  • Analysis of P-FAKSer732 levels in melanoma, ovarian, and thyroid tumor cell lines and ovarian cancer ascites.
  • Investigating the impact of EGFR/MEK/ERK axis activation on P-FAKSer732 levels during mitosis.
  • Assessing the role of P-FAKSer732 in microtubule dynamics, spindle assembly, and chromosome alignment using biochemical and cellular assays.
  • Utilizing roscovitine to inhibit CDK5 activity and evaluate its effect on mitosis.

Main Results:

  • P-FAKSer732 levels increase during mitosis, particularly upon EGFR/MEK/ERK activation, in an integrin-independent manner.
  • P-FAKSer732 is essential for maintaining proliferation rates and is inversely correlated with acetylated α-tubulin.
  • P-FAKSer732 localizes to and associates with microtubules, promoting their depolymerization and influencing mitotic spindle assembly and chromosome alignment.
  • EGFR activation increases P-FAKSer732 and polymerized microtubules, while CDK5 inhibition impairs mitotic processes.

Conclusions:

  • FAK plays a multifaceted role in neoplastic cells, extending beyond integrin-dependent migration to include integrin-independent regulation of microtubule dynamics and mitosis.
  • P-FAKSer732 is a critical regulator of mitotic progression and microtubule dynamics.
  • The EGFR/MEK/ERK/CDK5 pathway and P-FAKSer732 represent a promising therapeutic target for inhibiting tumor cell growth.

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...