Grb10 is a dual regulator of receptor tyrosine kinase signaling

Kabir, Nuzhat N.; Kazi, Julhash U.

doi:10.1007/s11033-014-3046-4

Cited by 29 publications

(22 citation statements)

References 70 publications

(57 reference statements)

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“…SOCS2 has higher affinity for the motifs pY-(I/L/V)-(I/L)-(I/V)-I and SOCS4 has higher affinity for the motifs pY-(I/L/V)-X-(I/V/S/T/G)-X [60]. Signaling through RTKs is tightly regulated by interacting proteins and very often SH2-domain containing proteins are involved in this regulation [4][5][6][7][106][107][108]. Since SH2 domain of different SOCS proteins displays specificity to the different pY consensus sequence it is expected that SOCS proteins display a degree of selectively in regulation of RTK signaling.…”

Section: Discussionmentioning

confidence: 99%

SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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SOCS proteins in regulation of receptor tyrosine kinase signaling.Uddin, Kazi; Kabir, Nuzhat N; Flores-Morales, Amilcar; Rönnstrand, Lars Link to publication Citation for published version (APA): Kazi, J. U., Kabir, N. N., Flores-Morales, A., & Rönnstrand, L. (2014). SOCS proteins in regulation of receptor tyrosine kinase signaling. Cellular and Molecular Life Sciences, 71(17), 3297-3310. DOI: 10.1007/s00018-014-1619-y General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractThe receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many of this family of kinases are overexpressed or mutated in human malignancies and thus became attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressor of cytokine signaling (SOCS) family proteins are well known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7 and CIS. A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs sometimes can bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways.

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Section: Discussionmentioning

confidence: 99%

SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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“…Signaling downstream of FLT3 is tightly controlled by various signaling proteins which associate with FLT3 and regulate downstream signaling by propagating the signals from extracellular stimuli or diminish the signal by destabilizing the receptor. For example, association of GRB10, SLAP, SYK and CSK resulted in enhanced FLT3 signaling, while the association of SOCS6, SOCS2 and LNK suppressed FLT3 signaling by destabilizing the receptor [85][86][87][88][89][90][91][92][93][94][95]. BEX1 expression was found to be down-regulated in a group of FLT3-ITD positive AML patients [8].…”

Section: Bex Proteins In Acute Myeloid Leukemia (Aml)mentioning

confidence: 97%

Brain-Expressed X-linked (BEX) proteins in human cancers

Kazi

Kabir

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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The Brain-Expressed X-linked (BEX) family proteins are comprised of five human proteins including BEX1, BEX2, BEX3, BEX4 and BEX5. BEX family proteins are expressed in a wide range of tissues and are known to play a role in neuronal development. Recent studies suggest a role of BEX family proteins in cancers. BEX1 expression is lost in a subgroup of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Expression of BEX1 controls cell surface receptor signaling and restores imatinib response in resistant cells. BEX2 is overexpressed in a group of breast cancer patients and also in gliomas. Increased BEX2 expression led to enhanced NF-κB signaling as well as cell proliferation. Although BEX2 acts as tumor promoter in a subset of breast cancer, BEX3 expression displayed an opposite role. Overexpression of BEX3 resulted in inhibition of tumor formation in breast cancer mouse xenograft models. The role of BEX4 and BEX5 in cancer has not yet been defined. Collectively this suggests that BEX family members have distinct roles in cancers.While BEX1 and BEX3 act as a tumor suppressors, BEX2 seems to act as an oncogene.

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“…In mouse and human, Grb10 has five major protein domains: the N-terminal proline-rich region (PR), a centrally located pleckstrin homology domain (PH), a Ras-associating domain (RA), a C-terminal Src homology 2 domain (SH2), and the familyspecific BPS domain, so named because it is between the PH and SH2 domains (4). Each domain is associated with protein binding partners that define the functions of Grb10 in development and growth ( Fig.…”

Section: Grb10 Binding Partners Define Its Role In Developmentmentioning

confidence: 99%

“…These proteins interact with numerous receptor tyrosine kinases, impacting a variety of signaling pathways (1). Specifically, Grb10 has been implicated in the regulation of cell proliferation, apoptosis, and metabolism, among other functions (2)(3)(4). The first characterized Grb10 knockout mouse exhibited overgrowth in numerous organs and tissues, suggesting that Grb10 acts as a potent growth suppressor in vivo (5).…”

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confidence: 99%

Tissue-specific regulation and function of Grb10 during growth and neuronal commitment

Plasschaert

Bartolomei

2014

Proc. Natl. Acad. Sci. U.S.A.

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Growth-factor receptor bound protein 10 (Grb10) is a signal adapter protein encoded by an imprinted gene that has roles in growth control, cellular proliferation, and insulin signaling. Additionally, Grb10 is critical for the normal behavior of the adult mouse. These functions are paralleled by Grb10’s unique tissue-specific imprinted expression; the paternal copy of Grb10 is expressed in a subset of neurons whereas the maternal copy is expressed in most other adult tissues in the mouse. The mechanism that underlies this switch between maternal and paternal expression is still unclear, as is the role for paternally expressed Grb10 in neurons. Here, we review recent work and present complementary data that contribute to the understanding of Grb10 gene regulation and function, with specific emphasis on growth and neuronal development. Additionally, we show that in vitro differentiation of mouse embryonic stem cells into alpha motor neurons recapitulates the switch from maternal to paternal expression observed during neuronal development in vivo. We postulate that this switch in allele-specific expression is related to the functional role of Grb10 in motor neurons and other neuronal tissues.

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Grb10 is a dual regulator of receptor tyrosine kinase signaling

Cited by 29 publications

References 70 publications

SOCS proteins in regulation of receptor tyrosine kinase signaling

SOCS proteins in regulation of receptor tyrosine kinase signaling

Brain-Expressed X-linked (BEX) proteins in human cancers

Tissue-specific regulation and function of Grb10 during growth and neuronal commitment

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